Pharmacokinetic and Pharmacodynamic Analysis of Amprena...

Pharmacokinetic and Pharmacodynamic Analysis of Amprenavir-Containing Combination Therapy in HIV-1-Infected Children

Pharmacokinetic and Pharmacodynamic Analysis of Amprenavir-Containing Combination Therapy in HIV-1-Infected Children
Nov 2004
Daniel S. Stein, Yu Lou, Mark Johnson, Sharon Randall, Stephane Blanche for the Prob2004 Study Team
Journal of Clinical Pharmacology
Abstract
Several factors influence the antiviral response to antiretroviral therapy. In this pharmacokinetic and pharmacodynamic analysis, the relationship of drug exposure, demographics, and cotherapy measures to antiviral response in a cohort of largely treatment-experienced children treated with amprenavir and nucleoside reverse transcriptase inhibitors was examined. Multiple pharmacodynamic and demographic factors were examined, but only the minimum plasma concentration (Cmin)/protein-binding-adjusted 50% inhibitory drug concentration (IC50) ratio and whether individuals received 2 versus fewer than 2 nucleosides to which their viral isolates were susceptible were associated with the magnitude of the time-weighted average change in HIV-1 RNA log10 copies/mL from baseline (AAUCMB). In multivariate logistic regression analysis, only the Cmin/IC50 ratio was independently associated with having a 1 log10 AAUCMB decline. The probability in the study population of having a 1log10 AAUCMB was 50% and 85% at Cmin/IC50 ratios of 1 and 4, respectively. Of the multiple factors examined, only the Cmin/IC50 ratio was a significant predictor of antiviral response in the first 8 weeks on amprenavir-containing combination antiretroviral therapy.
Key Words: Antiretroviral therapy ? amprenavir ? protease inhibitors ? nucleoside reverse transcriptase inhibitors ? HIV ? pharmacokinetics ? pediatrics
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