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  • 1. Carlsten, A
    et al.
    Waern, M
    Holmgren, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Allebeck, P
    The role of benzodiazepines in elderly suicides2003In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 31, no 3, p. 224-228Article in journal (Refereed)
    Abstract [en]

    Aims: In Sweden, suicides by drug poisoning have decreased in the population at large during the past two decades. However, drug poisoning suicides increased among the elderly during this period. Suicides by benzodiazepine poisoning increased in this age group despite a reduction in prescription sales of these drugs. This study aims therefore to determine the role of benzodiazepines in suicide late in life. Methods: Information concerning all definite suicides and deaths due to "undetermined" causes recorded among Swedish citizens aged 65 and above during 1992-96 was obtained from the Cause-of-Death Register. Death certificates were scrutinized to determine the type of drug employed in drug-related suicides. Results of the post mortem screening for drugs and alcohol were then examined. Results: A benzodiazepine was implicated in 216/548 (39%) of the drug poisoning suicides recorded among the elderly. Death certificates revealed that a benzodiazepine was the sole agent in 72% of these cases. Flunitrazepam or nitrazepam were implicated in 90% of the single benzodiazepine suicides. In addition to the suicides classified as drug poisonings, 82 cases were found in which a drug may have contributed to the cause of death. Benzodiazepines predominated. The terminal cause of death was drowning, often in the victim's own bathtub, in three-quarters of these cases. The annual fatality ratios for the newer benzodiazepine-like hypnotics zopiclone and zolpidem appear to be on the rise. Conclusion: Benzodiazepines, especially the hypnotics flunitrazepam and nitrazepam, are common in drug poisoning suicides in the elderly and should be prescribed with caution for this age group.

  • 2.
    Druid, Henrik
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Holmgren, Per
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    A compilation of fatal and control concentrations of drugs in postmortem femoral blood1997In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 42, no 1, p. 79-87Article in journal (Refereed)
    Abstract [en]

    A compilation of postmortem femoral blood concentrations of drugs is presented. The samples are collected from cases in which the cause of death was: A) certified intoxication by one substance alone, B) certified intoxication by more than one substance and/or alcohol, and C) certified other cause of death without incapacitation due to drugs. The concentrations were compared with blood concentrations detected in suspected drugged drivers (D), and with previously published fatal and therapeutic concentrations. The special features of this compilation are: 1) exclusively femoral blood concentrations are quoted, 2) all analyses are based on samples handled according to a standardized, quality-controlled procedure, 3) two control groups are included, and 4) one-substance-only intoxications are separated from other intoxications. The material is based on a selection of 15,800 samples sent to the Department of Forensic Chemistry in Linkoping, Sweden, during 1992 to 1995 from the six forensic pathology units in Sweden, and the list includes 83 drugs. The compilation includes drugs, where previously published data are scarce. Furthermore, the data gathered from cases with other cause of death than intoxication (group C) constitute a new kind of reference information, which probably offers a better estimate of obviously non fatal levels in postmortem blood than any compilation of therapeutic concentrations in living subjects. The possible factors influencing postmortem drug concentrations are discussed.

  • 3.
    Holmgren, Anita
    et al.
    Department of Forensic Genetics and Forensic Toxicology National Board of Forensic Medicine, Linköping.
    Holmgren, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    High re-arrest rates among drug-impaired drivers despite zero-tolerance legislation2008In: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 40, no 2, p. 534-540Article in journal (Refereed)
    Abstract [en]

    Background: A zero-tolerance law for driving under the influence of drugs (DUID) in Sweden led to a 10-fold increase in the number of cases submitted by the police for toxicological analysis. The statutory blood-alcohol concentration (BAC) limit for driving is 0.2 mg/g (∼0.02 g%). Methods: An in-house database (TOXBASE) was used to investigate re-arrests for impaired driving over 4 years (2001-2004), which comprised 36,799 cases. The age, gender, re-arrest rate of the offenders and the concentrations of ethanol and amphetamine in blood samples were evaluated. Results: We found that 44% of individuals (N = 16,277) re-offended 3.2 times on average (range 1-23 arrests). Between 85 and 89% of first-time offenders were men and there was also a male dominance among the recidivists (88-93%). The mean age of drunken drivers was ∼40 years compared with ∼35 years for driving under the influence of amphetamine, which was the drug identified in 50-60% of DUID cases, either alone or together with other licit or illicit drugs. The median BAC was 1.5 mg/g (∼0.15 g%), which suggests a dominance of heavy drinkers. The median BAC was even higher in recidivists (1.6-1.7 mg/g). The median concentration of amphetamine in blood was 1.0 mg/L in recidivists compared with 0.5 mg/L in the first-time offenders. About 14% of drunken drivers re-offended 1-10 times compared with 68% of DUID suspects, who were re-arrested 1-23 times. People with only a scheduled prescription drug in blood were re-arrested much less frequently (∼17%) compared with those taking illicit drugs (68%). Conclusions: The appreciable increase in number of arrests for DUID after a zero-tolerance law might reflect a heightened enthusiasm by the police authorities armed with knowledge that a prosecution is easier to obtain. Zero-tolerance laws do not deter people from impaired driving judging by the high re-arrest rates. During the sentencing of hardcore offenders, the courts should give more consideration to the underlying substance abuse problem. © 2007 Elsevier Ltd. All rights reserved.

  • 4.
    Holmgren, Per
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Postmortem toxicology: aspects on interpretation2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Postmortem toxicology is a matter of analytical chemistry and the consequent interpretation of the results. Thus, both parts are of great importance to come to the right conclusion or the most probable explanation of the analytical results. When interpreting toxicological results there are a lot of different aspects to consider, such as: were the analytical methods used appropriate and with acceptable accuracy, what specimen was analyzed and how was it collected and stored before the analysis, what concentration of a drug can be considered normal or "therapeutic" and which concentration is fatal. Other circumstance to consider is the stability of the drug substances, the pharmacokinetics and pharmacodynamics of the drugs, possible drug interactions, pharmacogenetics and postmortem redistribution.

    One crucial question in interpretation of postmortem toxicology results is to find reliable data on the significance of different drug concentrations. Instead of comparing concentrations found in postmortem blood with so called therapeutic concentrations in serum or plasma from the clinical setting, an inappropriate way that will lead to erroneous results, a new approach was used. Data was collected on drug concentrations in femoral blood from autopsy cases where the cause of death by certain not was intoxication and where the diseased was not incapacitated. These concentrations does not reflect any "therapeutic" concentration, which seldom is the key issue in postmortem toxicology, but represents concentrations which could be regarded as normally found and not associated with a fatal outcome. Applying this way to get reference concentrations, errors can be reduced and the problem associated with drug redistribution can be diminished.

    Normally samples are stored for one year or more and for a variety of drugs no concentration changes in femoral blood were noted when stored at -20° C with the exception of e.g. ethanol, tetrahydrocannabinol (THC) and zopiclone. Vitreous humor (VH) can be used as an alternative specimen to blood and there exists a correlation between the concentration in VH compared to the blood concentration and the degree of protein binding of the substances. VH can also be used to estimate the corresponding blood concentration under certain circumstances.

    Several drugs exist as racemate, containing two or several enantiomers. Chiral analysis can provide additional information about the time that has passed between intake of a drug and the time of death, thus improving the possibilities to predict whether an acute or chronic intake is at hand.

    Pharmacokinetic and pharmacodynamic interactions are issues of great importance and have a great impact on interpretation in postmortem toxicology. Pharmacogenetics is another issue that attracts more and more attention in forensic toxicology. Awareness and knowledge of these factors are of utmost importance in order to produce accurate interpretations of postmortem toxicology results.

    List of papers
    1. A compilation of fatal and control concentrations of drugs in postmortem femoral blood
    Open this publication in new window or tab >>A compilation of fatal and control concentrations of drugs in postmortem femoral blood
    1997 (English)In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 42, no 1, p. 79-87Article in journal (Refereed) Published
    Abstract [en]

    A compilation of postmortem femoral blood concentrations of drugs is presented. The samples are collected from cases in which the cause of death was: A) certified intoxication by one substance alone, B) certified intoxication by more than one substance and/or alcohol, and C) certified other cause of death without incapacitation due to drugs. The concentrations were compared with blood concentrations detected in suspected drugged drivers (D), and with previously published fatal and therapeutic concentrations. The special features of this compilation are: 1) exclusively femoral blood concentrations are quoted, 2) all analyses are based on samples handled according to a standardized, quality-controlled procedure, 3) two control groups are included, and 4) one-substance-only intoxications are separated from other intoxications. The material is based on a selection of 15,800 samples sent to the Department of Forensic Chemistry in Linkoping, Sweden, during 1992 to 1995 from the six forensic pathology units in Sweden, and the list includes 83 drugs. The compilation includes drugs, where previously published data are scarce. Furthermore, the data gathered from cases with other cause of death than intoxication (group C) constitute a new kind of reference information, which probably offers a better estimate of obviously non fatal levels in postmortem blood than any compilation of therapeutic concentrations in living subjects. The possible factors influencing postmortem drug concentrations are discussed.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85073 (URN)8988577 (PubMedID)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2017-12-07
    2. Stability of drugs in stored postmortem femoral blood and vitreous humor
    Open this publication in new window or tab >>Stability of drugs in stored postmortem femoral blood and vitreous humor
    2004 (English)In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 49, no 4, p. 820-825Article in journal (Refereed) Published
    Abstract [en]

    The stability of 46 drugs in postmortem femoral blood stored for one year at -20°C was investigated. The drugs included benzodiazepines, antidepressants, analgetics and hypnotics. For seven drugs we found a significant change in the concentration between the first and second analysis. Five substances; ethanol, desmethylmianserin, 7-amino-nitrazepam, THC and zopiclone showed a decrease in the concentration whereas the concentrations of two substances; ketobemidone and thioridazine increased. However, the changes observed were not of such an order that it would affect the interpretation in normal forensic casework. We also investigated the possible influence of potassium fluoride on the concentrations of the 46 drugs in vitreous humor after storage for one year. For two substances, ethanol and zopiclone, there were significantly lower concentrations in the samples without potassium fluoride. Furthermore, we also studied the correlation between the concentrations in femoral blood and vitreous humor. For 23 substances there was a significant difference between the concentrations in the vitreous humor and femoral blood. Significant correlations between the concentrations in these two specimens were found for 23 substances, indicating that vitreous humor can be an alternative specimen when blood samples are not available, provided that such correlation exists for the particular substance. Statistical analysis also revealed a correlation between the degree of protein binding of the different drugs and percentage of vitreous/femoral blood concentrations.

    Keywords
    forensic science; postmortem toxicology; stability; stored samples; vitreous humor; femoral blood
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53524 (URN)10.1520/JFS2003433 (DOI)
    Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2017-12-12
    3. Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19
    Open this publication in new window or tab >>Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19
    Show others...
    2004 (English)In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 2, p. 94-104Article in journal (Refereed) Published
    Abstract [en]

    Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13692 (URN)10.1093/jat/28.2.94 (DOI)
    Available from: 2003-06-20 Created: 2003-06-20 Last updated: 2017-12-13
    4. Drug interactions: a challenge in interpreting postmortem toxicology results and a problem in the clinical practice
    Open this publication in new window or tab >>Drug interactions: a challenge in interpreting postmortem toxicology results and a problem in the clinical practice
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Multiple drug intake is a problem in tbe clinical setting with potential to adverse drug reactions and certainly a problem in interpretation of forensic toxicology results. The aims of this investigation were to study the incidence of concomitant drugs in autopsy cases where citalopram or zopiclone were detected in femoral blood and to evaluate the potential of drug interactions.

    Methods: All medico-legal autopsy cases in Sweden during 1992 to 2003 where citalopram or zopiclone were detected in femoral blood at the toxicological analyses were selected. The number and occurrences of concomitant drugs were recorded together with the concentrations as well as the cause of death.

    Results: In the 2405 cases with citalopram, 123 different drugs, metabolites excluded, were detected 4679 times giving an average of 1.9 concomitant drugs and 1099 different dmg combinations were identified. The corresponding figures for the cases with zopiclone were 1557 cases, 118 different drugs detected 3984 times giving an average of 2.6 concomitant drugs and 977 different combinations. We found a strong positive correlation between the number of drugs detected and the frequency of cases judged to be intoxication.

    Conclusions: Pharmacokinetic and pharmacodynamic interactions are a potential problem when interpreting forensic toxicological results and the conclusions about the cause and manner of death in the single case must be based on all available information from the investigation and tbe autopsy and on tbe knowledge of tbe pharmacology of included drugs. A better control of prescriptions of what different drugs an individual is given together with a comprehensive therapy control may reduce the risks of adverse drug reactions and unintended or accidental intoxications.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85074 (URN)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2012-11-01
  • 5.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna-Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Dahl, Marja-Liisa
    Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden.
    Scordo, Maria Gabriella
    Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, University Hospital, Stockholm, Sweden.
    Druid, Henrik
    National Board of Forensic Medicine and Department of Forensic Medicine, Karolinska Institutet, Solna, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C192004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 2, p. 94-104Article in journal (Refereed)
    Abstract [en]

    Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.

  • 6.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Druid, Henrik
    Department of Forensic Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Drug interactions: a challenge in interpreting postmortem toxicology results and a problem in the clinical practiceManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Multiple drug intake is a problem in tbe clinical setting with potential to adverse drug reactions and certainly a problem in interpretation of forensic toxicology results. The aims of this investigation were to study the incidence of concomitant drugs in autopsy cases where citalopram or zopiclone were detected in femoral blood and to evaluate the potential of drug interactions.

    Methods: All medico-legal autopsy cases in Sweden during 1992 to 2003 where citalopram or zopiclone were detected in femoral blood at the toxicological analyses were selected. The number and occurrences of concomitant drugs were recorded together with the concentrations as well as the cause of death.

    Results: In the 2405 cases with citalopram, 123 different drugs, metabolites excluded, were detected 4679 times giving an average of 1.9 concomitant drugs and 1099 different dmg combinations were identified. The corresponding figures for the cases with zopiclone were 1557 cases, 118 different drugs detected 3984 times giving an average of 2.6 concomitant drugs and 977 different combinations. We found a strong positive correlation between the number of drugs detected and the frequency of cases judged to be intoxication.

    Conclusions: Pharmacokinetic and pharmacodynamic interactions are a potential problem when interpreting forensic toxicological results and the conclusions about the cause and manner of death in the single case must be based on all available information from the investigation and tbe autopsy and on tbe knowledge of tbe pharmacology of included drugs. A better control of prescriptions of what different drugs an individual is given together with a comprehensive therapy control may reduce the risks of adverse drug reactions and unintended or accidental intoxications.

  • 7.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Druid, Henrik
    National Board of Forensic Medicine, Department of Forensic Medicine, Karolinska Institutet, Stockholm, Sweden.
    Holmgren, Anita
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Stability of drugs in stored postmortem femoral blood and vitreous humor2004In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 49, no 4, p. 820-825Article in journal (Refereed)
    Abstract [en]

    The stability of 46 drugs in postmortem femoral blood stored for one year at -20°C was investigated. The drugs included benzodiazepines, antidepressants, analgetics and hypnotics. For seven drugs we found a significant change in the concentration between the first and second analysis. Five substances; ethanol, desmethylmianserin, 7-amino-nitrazepam, THC and zopiclone showed a decrease in the concentration whereas the concentrations of two substances; ketobemidone and thioridazine increased. However, the changes observed were not of such an order that it would affect the interpretation in normal forensic casework. We also investigated the possible influence of potassium fluoride on the concentrations of the 46 drugs in vitreous humor after storage for one year. For two substances, ethanol and zopiclone, there were significantly lower concentrations in the samples without potassium fluoride. Furthermore, we also studied the correlation between the concentrations in femoral blood and vitreous humor. For 23 substances there was a significant difference between the concentrations in the vitreous humor and femoral blood. Significant correlations between the concentrations in these two specimens were found for 23 substances, indicating that vitreous humor can be an alternative specimen when blood samples are not available, provided that such correlation exists for the particular substance. Statistical analysis also revealed a correlation between the degree of protein binding of the different drugs and percentage of vitreous/femoral blood concentrations.

  • 8.
    Holmgren, Per
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Holmgren, A
    Nationall Board of Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Alcohol and drugs in drivers fatally injured in traffic accidents in Sweden during the years 2000-20022005In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 151, no 1, p. 11-17Article in journal (Refereed)
    Abstract [en]

    During the years 2000-2002, alcohol, pharmaceuticals and illicit drugs were analysed in blood samples from fatally injured drivers in Sweden. The total number of drivers was 920 and in 855 of these, corresponding to 93%, a toxicological investigation was performed. About 85% of the drivers were men and 15% were women. All but three women (96%) were car drivers while the corresponding figure for men was about 78% and about 13% were motorcyclists. The number of positive cases increased from 38.9% in year 2000 to 45.9% in year 2002 and alcohol was the most common drug with frequencies of 19.8%, 25.0% and 21.8% for the studied years 2000, 2001 and 2002, respectively. The median blood alcohol concentration ranged from 1.6 to 2.0 mg/mL for men and from 1.2 to 1.8 mg/mL for women. There was a decrease in cases where alcohol was the only drug detected, from 52 out of 58 cases (90%) in year 2000 to 41 out of 61 cases (67%) in 2002. At the same time there was an increase, from 5.4% to 10.0% of illicit drugs, mainly amphetamine, and the cases with multiple drug intake increased from 10% to 26%. The prevalence of pharmaceuticals as the only drug or drugs detected decreased from 14.0% to 10.4% and in the majority of these cases the drug concentrations were within the therapeutic range.

  • 9.
    Holmgren, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Coexistence and concentrations of ethanol and diazepam in postmortem blood samples; Risk for enhanced toxicity?2003In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 48, p. 1416-1421Article in journal (Refereed)
  • 10.
    Holmgren, Per
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Norden-Pettersson, Lotta
    National Board of Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Caffeine fatalities - four case reports2004In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 139, no 1, p. 71-73Article in journal (Refereed)
    Abstract [en]

    Four cases of fatal intoxications with caffeine are described. Caffeine is widely available in beverages and in different OTC-products, in many of them in combinations with other drugs like ephedrine. Caffeine is not as harmless as one might believe. An overdose of caffeine alone, intentional or not, might be deadly. It seems to be warranted to include caffeine in the drug-screening of forensic autopsy cases. It is not motivated from a medical point of view to sell pure caffeine over the counter.

  • 11.
    Isacsson, G
    et al.
    Karolinska Institute.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides2005In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 111, no 4, p. 286-290Article in journal (Refereed)
    Abstract [en]

    To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents. Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26 422 cases of deaths by accident or natural causes in Sweden 1992-2000. There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group, SSRIs had lower relative risk in suicides compared with non-SSRIs. The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.

  • 12.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Holmgren, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Comparison of blood-ethanol concentration in deaths attributed to acute alcohol poisoning and chronic alcoholism2003In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 48, no 4, p. 874-879Article in journal (Refereed)
    Abstract [en]

    Ethanol concentrations were measured in femoral venous blood in deaths attributed to acute alcohol poisoning (N = 693) or chronic alcoholism (N = 825), according to the forensic pathology report. Among acute alcohol poisonings were 529 men (76%) with mean age 53 years and 164 women (24%) with mean age 53 years. In the chronic alcoholism deaths were 705 men (85%) with mean age 55 years and 120 women (15%) with mean age 57 years. The blood-ethanol concentrations were not related to the person's age (r = -0.17 in acute poisonings and r = -0.09 in chronic alcoholism). The distribution of blood-ethanol concentrations in acute poisoning cases agreed with a normal or Gaussian curve with mean, median, standard deviation, coefficient of variation, and spread of 0.36 g/100 mL, 0.36 g/100 mL, 0.086 g/100 mL, 24% and 0.074 to 0.68 g/100 mL, respectively. The corresponding concentrations of ethanol in chronic alcoholism deaths were not normally distributed and showed a mode between 0.01 and 0.05 g/100 mL and mean, median, and spread of 0.172 g/100 mL, 0.150 g/100 mL, and 0.01 to 0.56 g/100 mL, respectively. The 5th and 95th percentiles for blood-ethanol concentration in acute poisoning deaths were 0.22 and 0.50 g/100 mL, respectively. However, these values are probably conservative estimates of the highest blood-ethanol concentrations before death owing to metabolism of ethanol until the time of death. In 98 chronic alcoholism deaths (12%) there was an elevated concentration of acetone in the blood (> 0.01 g/100 mL), and 50 of these (6%) also had elevated isopropanol (>0.01 g/100 mL). This compares with 28 cases (4%) with elevated blood-acetone in the acute poisoning deaths and 22 (3%) with elevated blood-isopropanol. We offer various explanations for the differences in blood-ethanol and blood-acetone in acute poisoning and alcoholism deaths such as chronic tolerance, alcohol-related organ and tissue damage (cirrhosis, pancreatitis), positional asphyxia or suffocation by inhalation of vomit, exposure to cold coupled with alcohol-induced hypothermia, as well as various metabolic disturbances such as hypoglycemia and ketoacidosis.

  • 13.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Holmgren, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism2003In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 135, no 3, p. 206-212Article in journal (Refereed)
    Abstract [en]

    The concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N=628) or chronic alcoholism (N=647). In alcohol poisoning deaths both UAC and BAC were higher by about 2g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean-standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18-0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74g/l (N=457) the mean-S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30-0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74g/l (N=190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r=0.84, residual S.D.=0.47g/l) and in chronic alcoholism deaths (r=0.95, residual S.D.=0.41g/l). For both causes of death (N=1275), the correlation between BAC and UAC was r=0.95 and the residual S.D. was 0.46g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18:1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30:1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.

  • 14.
    Jönsson, Anna
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Fatal intoxications in a Swedish forensic autopsy material during 1992-20022004In: Forensic Science International, ISSN 0379-0738, Vol. 143, no 1, p. 53-59Article in journal (Refereed)
    Abstract [en]

    Compilations of substances detected in fatal intoxications are important in order to observe changes in intoxication patterns, to monitor effects of preventive work and to discover new trends in drug usage. The aim of the present study was to describe the current pattern of substances detected in fatal intoxications in Sweden. Fatal intoxications investigated at the Department of Forensic Chemistry, Linköping, Sweden, during 1992–2002, were analysed. All suicides, uncertain cases and accidents where the cause of death were fatal intoxications (ICD-9: E950, E980 and E859) were included and substances detected in more than 50 fatal intoxications (in femoral blood) were listed. For each substance, a cut off value was set, above which concentrations were considered toxic. Fatal intoxications were detected by forensic-chemical analyses in 12% (6998/60,314) of the forensic autopsies during the study period. Among the suicides, an average of 3.8 substances were detected per case, the corresponding figure for uncertain cases and accidents were 3.5 and 4.1 substances, respectively. Ethanol was by far the most frequently detected substance, detected in 43% (3039) of the fatal intoxications, of which 32% (960) had toxic concentrations, followed by propoxyphene, detected in 27% (1863) of the fatal intoxications of which 74% (1370) had toxic concentrations. The number of cases where ethanol and propoxyphene were detected decreased during the study period. Moreover, other CNS-active drugs such as antidepressants, analgesics and anxiolytics were also frequently detected. The drugs with high proportions of cases with toxic concentrations detected were propoxyphene, amitriptyline, zolpidem, carisoprodol, alprazolam, thioridazine, methadone and ketobemidone. Selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) were detected in 12% (833) and 10% (665), respectively. A significantly (P<0.001) higher proportion of cases where TCA were detected had toxic concentrations when compared with cases where SSRI were detected (64% versus 31%).

  • 15.
    Jönsson, Anna
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology. National Board of Forensic Medicine, Linköping, Sweden.
    Holmgren, Per
    National Board of Forensic Medicine, Linköping, Sweden.
    Druid, Henrik
    KI, Stockholm.
    Ahlner, Johan
    National Board of Forensic Medicine, Linköping, Sweden.
    Cause of death and drug use pattern in deceased drug addicts in Sweden, 2002-20032007In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 169, no 2-3, p. 101-107Article in journal (Refereed)
    Abstract [en]

    Compared with their contemporaries, individuals abusing illicit drugs suffer a higher risk of premature death. In Sweden, a simple protocol for registration of fatalities among abusers of alcohol, pharmaceuticals, illicit drugs, or other substances, has been used by the forensic pathologists since 2001. This routine was introduced to allow for an evaluation of the cause and manner of death, and patterns of abuse among different groups of abusers. We explored the data on drug abusers (i.e. abusers of illicit drugs) subjected to a forensic autopsy 2002-2003. The Swedish forensic pathologists examined 10,273 dead victims during the study period and 7% (743/10,273) of the cases were classified as drug abusers. Toxicological analyses were carried out in 99% (736/743) and illicit drugs were detected in 70% (514/736) of these. On average, 3.8 substances (legal or illegal) were found per case. The most common substances were ethanol and morphine, detected in 43 and 35% of the cases, respectively. When exploring the importance of the different substances for the cause of death, we found that the detection of some substances, such as fentanyl and morphine, strongly indicated a poisoning, whereas certain other substances, such as benzodiazepines more often were incidental findings. In total, 50% (372/743) died of poisoning, whereas only 22% (161/743) died of natural causes. Death was considered to be directly or indirectly due to drug abuse in 47% (346/743), whereas evidence of drug abuse was an incidental finding in 21% (153/743) or based on case history alone in 33% (244/743). We believe that this strategy to prospectively categorize deaths among drug addicts constitutes a simple means of standardizing the surveillance of the death toll among drug addicts that could allow for comparisons over time and between countries. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 16.
    Kugelberg, Fredrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Holmgren, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Druid, Henrik
    Stockholm.
    Codeine and morphine blood concentrations increase during blood loss2003In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 48, no 3, p. 664-667Article in journal (Refereed)
    Abstract [en]

    During extensive blood loss, a plasma volume refill will take place by transfer of extravascular fluid into the circulation. Drugs present in this fluid may follow and cause a rise or a drop in blood drug concentration, depending on their levels and accessibility in the restoration fluid. This study explored the possible changes of codeine, and its metabolite morphine, in whole blood during a standardized exsanguination in the rat. Three doses containing 5 mg codeine were given orally. In eight rats, blood loss was accomplished by slowly withdrawing 0.8 mL blood at 10 min intervals during 70 min. In control rats, blood was withdrawn only at 0 and 70 min. At 70 min, the final/initial codeine and morphine concentration ratios were 0.70 +/- 0.38 and 0.88 +/- 0.47, respectively, in controls, but increased to 1.28 +/- 0.44 (p=0.014) and 1.41 +/- 0.34 (p=0.021), respectively, in exsanguinated rats. It is concluded that blood loss can affect blood drug concentrations.

  • 17.
    Nordgren, Helena K
    et al.
    Karolinska Institutet.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Liljeberg, Paula
    Karolinska Institutet.
    Eriksson, Nadja
    Karolinska Institutet.
    Beck, Olof
    Karolinska Institutet.
    Application of direct urine LC-MS-MS analysis for screening of novel substances in drug abusers2005In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 29, no 4, p. 234-239Article in journal (Refereed)
    Abstract [en]

    A newly developed liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was used to study 3000 human urine samples from 3 different populations for 23 analytes covering phenylethylamines, benzylpiperazine, and non-benzodiazepine hypnotics. Direct injection of urine and LC-MS-MS with rapid chromatography and atmospheric pressure chemical ionization was used in the screening step. The cutoff levels were chosen to be at the limit of detection for most analytes to identify as many positive samples as possible. Typically one ion transition was monitored from the pseudo-molecular ions in the multiple reaction monitoring mode. Of the 797 positive screening findings, 518 (65%) were confirmed by a second LC-MS-MS analysis including solid-phase extraction. Confirmed analytical findings included 22 cases positive for N-benzylpiperazine, 88 for 3,4-methylenedioxy-N-methylamphetamine and metabolites, 4 for 1-phenyl-2-butylamine, 24 for zolpidem and metabolites, 118 for zopiclone and metabolites, and 1 for zaleplon. In conclusion, LC-MS-MS was found to be a robust alternative for drugs of abuse screening, offering high sensitivity compared with immunochemical screening methodology.

  • 18.
    Petersson, A.
    et al.
    Department of Forensic Medicine, Karolinska Institute, Sweden.
    Garle, M.
    Department of Pharmacology, Huddinge University Hospital, Doping Laboratory, Sweden.
    Holmgren, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology .
    Druid, H.
    Department of Forensic Medicine, Karolinska Institute, Sweden.
    Krantz, P.
    Department of Forensic Medicine, Lund University Hospital, Sweden.
    Thiblin, I.
    Department of Forensic Medicine, Uppsala University, Dag Hammarskjöds v 17, S-752 37 Uppsala, Sweden.
    Toxicological findings and manner of death in autopsied users of anabolic androgenic steroids2006In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 81, no 3, p. 241-249Article in journal (Refereed)
    Abstract [en]

    With the aim to characterize patterns in toxicological profile and manner of death in deceased users of anabolic androgenic steroids (AAS), a retrospective autopsy protocol study of 52 deceased users of AAS was undertaken. The AAS users were compared to 68 deceased users of amphetamine and/or heroin who were consecutively tested and found to be negative for AAS. Use of AAS was in the majority of cases (79%) associated with concomitant use of psychotropic substances. AAS-related deaths differed in several respects from deaths among users of heroin or amphetamine, most strikingly with regard to: (a) the median age at death, which was significantly lower for AAS users (24.5 years) than for users of heroin and/or amphetamine (34 and 40 years, respectively), (b) the manner of death, with AAS users dying significantly more often from homicide or suicide than users of other drugs, and (c) the body mass index (BMI), with AAS users exhibiting significantly higher BMI than users of other drugs. These results support the earlier reported association between use of AAS and use of other psychoactive substances. In addition, the data suggest that AAS users are more likely to become involved in incidents leading to violent death and have a higher risk of dying at a younger age than users of other drugs. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 19.
    Steentoft, A
    et al.
    University of Copenhagen.
    Teige, B
    University of Oslo.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Vuori, E
    University of Helsinki.
    Kristinsson, J
    University of Iceland.
    Hansen, A. C.
    University of Aarhus.
    Ceder, Gun
    Linköping University, Department of Medicine and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Wethe, G
    Norwegian Institute of Public Health.
    Rollmann, D
    University of Odense.
    Fatal poisoning in Nordic drug addicts in 20022006In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 160, no 03-Feb, p. 148-156Article in journal (Refereed)
    Abstract [en]

    The present study from 2002 includes medicolegally examined fatal poisonings among drug addicts in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition "drug addict" is applied by the participating countries. The number of deaths, age, sex, place of death, main intoxicant and other drugs present in the blood are recorded in order to obtain national data, as well as comparable Nordic data and data comparable to earlier studies from 1997 and 1991. The Icelandic results are commented on separately due to the low number of cases The most fatal overdoses are seen in Norway, in both the death rate (number per 100,000 inhabitants = 8.44) and in absolute number (n = 232). The comparable figures for the other four countries are Denmark 5.43 (n = 175), Iceland 3.6 (n = 6), Finland 2.93 (n = 94) and Sweden 2.56 (n = 136). In earlier studies from 1991 and 1997, the highest death rate is seen in Denmark, with Norway as number two. Denmark is the only country where the death rate decreases from 1997 to 2002. A relatively large increase in deaths in the younger age groups(less than 30 years) is noted from 1997 to 2002, except in Denmark, where only a small increase in overdose deaths in very young people (15-19 years) is observed. Females account for 12-20% of the overdoses (three out of six deaths in Iceland). Relatively fewer deaths are recorded in the capital areas in 2002 than in 1997 and 199 1, suggesting more geographically widespread drug use in the Nordic countries Heroin/morphine is the single most frequently encountered main intoxicant, varying from 10% of the cases in Finland to 72% of the cases in Norway. Finland differs from the other countries in that a high percentage of the fatal overdoses in Finland are not caused by an illicit drug; buprenorphine, overdoses are seen, and relatively few deaths resulting from heroin are seen. Methadone is the main intoxicant in 41% of the Danish overdose cases, 15% of the Norwegian cases, 4% of the Swedish cases and none of the Finnish overdose cases, an observation probably linked to different national prescription rules for methadone The analytical screening reveals extended polydrug use. Frequently seen substances, in addition to the main intoxicant are amphetamine, tetrahydrocannabinol (THC), benzodiazepines and ethanol.

  • 20.
    Wikström, M
    et al.
    National Board of Forensic Medicine.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    A2 (N-benzylpiperazine) a new drug of abuse in Sweden2004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 1, p. 67-70Article in journal (Refereed)
    Abstract [en]

    N-Benzylpiperazine was tested in the beginning of the 1970s as a possible antidepressant drug. However, in both animal and human studies, it was shown to possess amphetamine-like properties, and any further studies were stopped. In a forensic autopsy case in 1999, we found a substance so far unknown to us in the chromatogram of our method used for amphetamines. We could swiftly identify this compound as N-benzylpiperazine because of information given to us by a newly formed network comprising, among others, customs and the police. Since then, we have found N-benzylpiperazine in several cases, among them 11 cases from a number of prisons.

  • 21.
    Zackrisson, Anna-Lena
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Gladh, Ann-Britt
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fatal intoxication cases: cytochrome P450 2D6 and 2C19 genotype distributions2004In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 60, no 8, p. 547-552Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Many commonly used pharmaceuticals, such as antidepressants and neuroleptics as well as some illegal drugs, are metabolised by the cytochrome P450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Of Caucasians, 7-10% lack this enzyme, which can, upon administration of drugs in normal therapeutic doses, lead to adverse reactions and unexpected intoxication, leading in turn even to a fatal outcome in some cases.

    METHODS: Individuals (n=242) who had died due to intoxication by pharmaceuticals were genotyped for CYP2D6 and CYP2C19 and compared with a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. Four CYP2C19 alleles *1 (wt), *2, *3 and *4 were also identified by SNP analysis.

    RESULTS: The prevalence of the CYP2D6 poor metaboliser (PM) genotypes in individuals with fatal intoxication was lower (4.7%) than expected from the frequencies of these genotypes in the blood donors (8.5%). A significantly lower frequency P<0.005 (0.03 with correction according to Bonferroni) was found for the CYP2D6*4 allele among the fatal intoxication cases. The CYP2C19 genotype analyses showed the same results for the fatal intoxication cases and for the blood donors.

    CONCLUSIONS: The findings in this study confirm our earlier observations of a lower frequency of CYP2D6 PM genotypes in cases of fatal intoxication. To our knowledge, it has not been shown previously that intoxication victims might have a lower frequency of PMs than the general population.

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