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Pharmacokinetic and Pharmacodynamic Analysis of Amprenavir‐Containing Combination Therapy in HIV‐1—Infected Children
Author(s) -
Stein Daniel S.,
Lou Yu,
Johnson Mark,
Randall Sharon,
Blanche Stephane
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004269561
Subject(s) - amprenavir , pharmacodynamics , medicine , pharmacokinetics , pharmacology , population , combination therapy , immunology , biology , biochemistry , protease , environmental health , hiv 1 protease , enzyme
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 (C min )/protein‐binding‐adjusted 50% inhibitory drug concentration (IC 50 ) 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 log 10 copies/mL from baseline (AAUCMB). In multivariate logistic regression analysis, only the C min /IC 50 ratio was independently associated with having a 1 log 10 AAUCMB decline. The probability in the study population of having a 1 log 10 AAUCMB was 50% and 85% at C min /IC 50 ratios of ± 1 and 4, respectively. Of the multiple factors examined, only the C min /IC 50 ratio was a significant predictor of antiviral response in the first 8 weeks on amprenavir‐containing combination antiretroviral therapy.