Population pharmacokinetics of indinavir in patients infected with human immunodeficiency virus

Details

Serval ID
serval:BIB_1C445DFD3180
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Population pharmacokinetics of indinavir in patients infected with human immunodeficiency virus
Journal
Antimicrobial Agents and Chemotherapy
Author(s)
Csajka  C., Marzolini  C., Fattinger  K., Decosterd  L. A., Telenti  A., Biollaz  J., Buclin  T.
ISSN
0066-4804 (Print)
Publication state
Published
Issued date
09/2004
Volume
48
Number
9
Pages
3226-32
Notes
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
Indinavir is currently used at a fixed dose of 800 mg either three times a day or twice a day in combination with 100 mg of ritonavir. Dosage individualization based on plasma concentration monitoring might, however, be indicated. This study aimed to assess the pharmacokinetic profile of indinavir in patients infected with human immunodeficiency virus to characterize interpatient and intrapatient variability and to build up a Bayesian approach for dosage adaptation. A population analysis was performed with the NONMEM computer program with 569 plasma samples from a cohort of 239 unselected patients receiving indinavir. A one-compartment model with first-order absorption was adapted, and the influences of clinical characteristics on oral clearance (CL) and distribution volume (V) were examined. Predicted average drug exposure and trough and peak concentrations were derived for each patient and correlated with efficacy and toxicity markers. The population estimates of CL were 32.4 liters/h for female and 42.0 liters/h for male patients; oral V was 65.7 liters; and the rate constant of absorption (K(a)) was 1.0 h(-1). CL decreased by 63% with ritonavir intake and was moderately correlated to body weight. Both interpatient variability, best assigned to oral CL (coefficient of variation [CV], 39%) and K(a) (CV, 67%), and intrapatient variability were large (CV, 41%; standard deviation, 670 microg/liter). In conclusion, initial indinavir dosage should be decided according to ritonavir intake and sex, prior to plasma concentration measurements. The high interpatient pharmacokinetic variability represents an argument for therapeutic drug monitoring.
Keywords
Adolescent Adult Aged Algorithms Bayes Theorem Drug Monitoring Female HIV Infections/drug therapy/*metabolism HIV Protease Inhibitors/administration & dosage/*pharmacokinetics/therapeutic use Humans Indinavir/administration & dosage/*pharmacokinetics/therapeutic use Male Middle Aged Models, Biological Population
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 10:48
Last modification date
20/08/2019 12:52
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