Intracellular indinavir pharmacokinetics in HIV-infected patients: Comparison with plasma pharmacokinetics

Abstract

Objective: To determine intracellular concentrations of indinavir (IDV) and investigate the relationship between plasma and intracellular IDV pharmacokinetics in HIV-infected patients. Methods: A pharmacokinetic study of 10 patients receiving IDV plus dual nucleoside analogue therapy. Peripheral blood mononuclear cells were isolated by density gradient centrifugation and cell counts estimated. IDV was extracted from cells in the presence of 60% methanol and evaporated to dryness. Both plasma and intracellular IDV samples were assayed by high performance liquid chromatography linked to mass spectrometry. Data were subjected to non-compartmental pharmacokinetic analysis. Results: The mean intracellular IDV area under the curve over 8 h (AUC0-8) was lower than the plasma AUC0-8 (7574 ±1003 vs 25 060 ±171 ng/ml/h; P