Lopinavir/ritonavir combined with twice-daily 400 mg indinavir: pharmacokinetics and pharmacodynamics in blood, CSF and semen

Abstract

Objectives: To evaluate the steady-state blood plasma (BP), CSF and seminal plasma (SP) pharmacokinetics (PK) of twice-daily indinavir 400 mg and lopinavir/ritonavir. Methods: Ten HIV-1-positive men on lopinavir/ritonavir participated in a PK study. PK sampling was performed before and 2 weeks after adding indinavir to lopinavir/ritonavir-containing regimens. BP, CSF and SP RNA levels, CD4 counts and blood chemistry were checked at baseline and 2 weeks after indinavir. Results: At baseline: lopinavir parameters (n=10) in BP were within expected levels. Median lopinavir trough concentrations (n=5) in CSF and SP were below the limit of detection (BLD) (i.e. C_max, C_min and AUC_0–12 increased by 9%, 46% and 20%, respectively (PPPC_max 3365 ng/mL (range 2130–5194), C_min 293 ng/mL (14–766), T_max 2.25 h (1–3), AUC_0–12 22452 ng/mL·h (11243–33661), and t_1/2 2.8 h (1.4–3.7). Median indinavir concentrations in CSF and SP were 39 ng/mL (21–86) and 592 ng/mL (96–983). Two of eight men who initially had detectable BP viral load (VL) became BLD (80 ng/mL in seven of eight plasma samples, and all CSF and semen samples collected.