liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Pharmacokinetics and pharmacodynamics of aminoglycosides
Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
1992 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The pharmacokinetics of amikacin in humans and the pharmacodynamic effects, i.e. initial killing and postantibiotic effect (P AE), of the aminoglycosides were studied in this thesis. For1y-five elderly patients with serious infections were treated in a prospective, comparative and randomized pharmacokinetic study with amikacin given once or twice daily. The administration of a single dose of 15 mg!kg of amikacin yielded a higher peak concentration (55 mg/1) in comparison to the peak concentration (33 mg!l) when the same total dose was given twice daily. The area under the curve (AUC) was the same regardless of the mode of administration. The kinetics of amikacin, 11 mg/kg and 15 mg/kg were studied during a 24 h interval. Using a hiexponential equation the average serum half-lives were quite long, 4.4 - 5.2 h. In practice, a uni-exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. When given to our elderly patients the peak concentration of 11 mg/kg of arnikacin ( 42 mg!l) seems to be sufficiently high in relation to the MICs of important isolated pathogens, i.e. ,2>10 x MIC. Thus this dose may be sufficient for elderly patients when given once daily. The in vitro postantibiotic effects (P AE) of amikacin, gentamicin, netilmicin and tobramycin onGram-negative bacteria and on staphylococci were studied by a bioluminescent assay of bacterial ATP. This method simplified the P AE studies and made such studies possible at high aminoglycoside concentrations. The length of the P AE was concentration-dependent for all the aminoglycosides studied. The mean P AE values of the Gram-negative strains and of the Staphylococcus aureus strains ranged between 3 to 7 h at the aminoglycoside concentrations normally reached in serum during standard dosing. The P AE of arnikacin alone, and in combination with ceftazidime, ceftriaxone or piperacillin, on Gram-negative bacteria and on enterococci was also studied. The combination of 13-lactam antibiotics with amikacin induced longer P AEs than the sum of P AEs of the individual drugs. This synergistic P AE was seen especially when the 13-lactam antibiotics were combined with amikacin concentrations close to MIC. Amikacin alone induced no P AEon the Enterococcus .faecalis strains. APAE of 1.6 h at the most resulted from exposure to piperacillin. In combination, amikacin and piperacillin increased the P AE to 5.5 h. In conclusion, with regard to the pharmacokinetics and the pharmacodynamics there is strong support for the once daily dosing regimens of aminoglycosides. The results of this study could also haveimpact on dosing regimens of antimicrobial combinations and might lead to administration of lower doses of potentially toxic drugs without loss of efficacy.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1992. , 59 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 365
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-28582Local ID: 13736ISBN: 91-7870-901-6OAI: diva2:249393
Public defence
1992-06-12, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-07-19Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Isacsson, Barbro
By organisation
Infectious DiseasesClinical MicrobiologyFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 291 hits
ReferencesLink to record
Permanent link

Direct link