Journal Article

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

Adil Isaac, Stephen Taylor, Patricia Cane, Erasmus Smit, Sarah E. Gibbons, David J. White, Susan M. Drake, Saye Khoo and David J. Back

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 54, issue 2, pages 498-502
Published in print August 2004 | ISSN: 0305-7453
Published online August 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh357
Lopinavir/ritonavir combined with twice-daily 400 mg indinavir: pharmacokinetics and pharmacodynamics in blood, CSF and semen

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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. <10 ng/mL) and 248 ng/mL (range 96–2777), respectively. After indinavir: lopinavir Cmax, Cmin and AUC0–12 increased by 9%, 46% and 20%, respectively (P<0.32, P<0.32 and P<0.20). In two of four men lopinavir concentrations in CSF were detectable at 27 and 29 ng/mL. Median SP lopinavir concentration was 655 ng/mL (20–2734). Median indinavir PK parameters were Cmax 3365 ng/mL (range 2130–5194), Cmin 293 ng/mL (14–766), Tmax 2.25 h (1–3), AUC0–12 22452 ng/mL·h (11243–33661), and t1/2 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 (<50 copies/mL) after the addition of indinavir, and in 2/4 men with low-level viraemia in SP (BPVL BLD) their SPVL became BLD after addition of indinavir.

Conclusions: Adding indinavir 400 mg twice daily to lopinavir/ritonavir-containing regimens did not significantly alter the median lopinavir PK parameters. However, wide interpatient variability in lopinavir concentrations was seen. In contrast plasma indinavir levels were >80 ng/mL in seven of eight plasma samples, and all CSF and semen samples collected.

Keywords: sanctuary sites; double boosted; protease inhibitors; drug interactions; HIV

Journal Article.  2562 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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