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Pharmacogenetic aspects of tramadol pharmacokinetics and pharmacodynamics after a single oral dose
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
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2014 (English)In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 238, 125-132 p.Article in journal (Refereed) Published
Abstract [en]

The major purpose of this study was to elucidate if genotyping can facilitate interpretations of tramadol (TRA) in forensic case work, with special regard to the estimation of the time of drug intake and drug related symptoms (DRS). The association between genetic polymorphisms in CYP2D6, OPRM1 and ABCB1 and pharmacokinetic and pharmacodynamic properties of TRA was studied. Nineteen healthy volunteers were randomized into two groups receiving a single dose of either 50 or 100 mg of orally administrated TRA. Blood samples were collected prior to dosing and up to 72 h after drug intake. The subjects were asked to report DRS during the experimental day. We found a positive correlation between the metabolic ratio of O-desmethyltramadol (ODT) to TRA and the time after drug intake for both CYP2D6 intermediate metabolizers and extensive metabolizers. For the only poor metabolizer with detectable ODT levels the metabolic ratio was almost constant. Significant associations were found between the area under the concentration-time curve (AUC) and three of the investigated ABCB1 single nucleotide polymorphisms for TRA, but not for ODT and only in the 50 mg dosage group. There was great interindividual variation in DRS, some subjects exhibited no symptoms at all whereas one subject both fainted and vomited after a single therapeutic dose. However, no associations could be found between DRS and investigated polymorphisms. We conclude that the metabolic ratio of ODT/TRA may be used for estimation of the time of drug intake, but only when the CYP2D6 genotype is known and taken into consideration. The influence of genetic polymorphisms in ABCB1 and OPRM1 requires further study.

Place, publisher, year, edition, pages
Elsevier, 2014. Vol. 238, 125-132 p.
Keyword [en]
Tramadol; Pharmacokinetics; Pharmacodynamics; CYP2D6; ABCB1; OPRM1
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-106838DOI: 10.1016/j.forsciint.2014.03.003ISI: 000334580700025PubMedID: 24709712OAI: oai:DiVA.org:liu-106838DiVA: diva2:720137
Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2017-12-05Bibliographically approved

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Bastami, SalumehHaage, PernillaKronstrand, RobertKugelberg, FredrikZackrisson, Anna-LenaUppugunduri, Srinivas

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Bastami, SalumehHaage, PernillaKronstrand, RobertKugelberg, FredrikZackrisson, Anna-LenaUppugunduri, Srinivas
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Division of Drug ResearchFaculty of Health SciencesDivision of Microbiology and Molecular MedicineDepartment of Clinical Chemistry
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