Within-Patient Atazanavir Trough Concentration Monitoring in HIV-1-Infected Patients

Abstract

Objective: Protease inhibitors (PIs) exhibit considerable interpatient pharmacokinetic variability in plasma trough concentrations. Therapeutic drug monitoring (TDM) is occasionally used to guide chronic dosing to achieve target trough concentrations, but its clinical success assumes minimal intrasubject variability. Therefore, our primary objective was to evaluate intrapatient variability in atazanavir (ATV) plasma trough concentrations in HIV-1-infected patients. Design/Methods: In a single-site, prospective, cohort study, patients on atazanavir with or without ritonavir (ATV/r or ATV) for 2 clinic visits were enrolled. Adherence and time since last dose (TSLD) were verified at each visit. ATV was assayed with high-performance liquid chromatography. Intra- and interpatient variation was evaluated using the median intraindividual percentage coefficient of variation (ICV). Results: The mean 24-hour ATV trough concentrations for the first and second visit for the ATV/r group (n = 10) was 598 (CV 84%) and 525 ng/mL (CV 66%), respectively (P = .511), and 300 (CV 81%) and 434 ng/mL (CV 106%) for the ATV group (n = 4), respectively (P = .369). Median ICV was 43.1% for all patients (range: 0.6%-107.6%), 38.1% (0.6%-107.6%) for the ATV/r group, and 33.1% (2.3%-87.6%) for the ATV group. Conclusions: Potential intrapatient variability in ATV troughs suggests that repeated measurements may be required to ensure that target values are maintained.

Keywords

atazanavir therapeutic drug monitoring pharmacokinetics protease inhibitors pharmacodynamics

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