Document Detail


Effect of a single dose of ritonavir on the pharmacokinetic behavior of elvucitabine, a nucleoside reverse transcriptase inhibitor, administered in healthy volunteers.
MedLine Citation:
PMID:  19015353     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to determine the effect of a single dose of 300 mg of ritonavir on the plasma pharmacokinetics (PK) of a single dose of 20 mg of elvucitabine when the two drugs were coadministered in healthy subjects. In a three-way crossover design, 30 subjects received 20 mg of elvucitabine, 300 mg of ritonavir, or 20 mg of elvucitabine coadministered with 300 mg of ritonavir. Elvucitabine concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. The PK of elvucitabine was determined using both noncompartmental and compartmental analyses. Models were developed and tested using ADAPT-II, while a population analysis was performed using IT2S. Comparisons of PK parameters between groups were done with SAS. The pharmacokinetic behavior of elvucitabine was best described by a two-compartment linear model using two absorption rates and a first-order elimination rate. Ritonavir significantly impacted the PK of elvucitabine by reducing elvucitabine's bioavailability, with the most plausible explanation being an inhibition on influx transporters by ritonavir. The decrease in elvucitabine bioavailability when elvucitabine was coadministered with ritonavir may be due to ritonavir's inhibiting influx gut transporters. Continued development of elvucitabine is warranted to better characterize its PK and to determine its in vivo efficacy against human immunodeficiency virus.
Authors:
Philippe Colucci; John C Pottage; Heather Robison; Jacques Turgeon; Murray P Ducharme
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial     Date:  2008-11-17
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  53     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-23     Completed Date:  2009-04-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  646-50     Citation Subset:  IM    
Affiliation:
University of Montreal, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / pharmacology*
Area Under Curve
Binding, Competitive / drug effects
Biological Availability
Cross-Over Studies
Drug Interactions
Female
Humans
Intestinal Absorption / physiology
Linear Models
Male
Middle Aged
Population
Reverse Transcriptase Inhibitors / pharmacokinetics*
Ritonavir / pharmacology*
Tandem Mass Spectrometry
Young Adult
Zalcitabine / analogs & derivatives*,  pharmacokinetics
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Reverse Transcriptase Inhibitors; 0/Ritonavir; 134379-77-4/dexelvucitabine; 7481-89-2/Zalcitabine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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