JAC Advance Access originally published online on July 14, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(2):498-502; doi:10.1093/jac/dkh357
JAC vol.54 no.2 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.
Lopinavir/ritonavir combined with twice-daily 400 mg indinavir: pharmacokinetics and pharmacodynamics in blood, CSF and semen
1 Hawthorne House, Department of Genitourinary Medicine, Birmingham Heartlands Hospital, Birmingham B9 5SS; 2 Health Protection Agency, Birmingham Heartlands Hospital, Birmingham, Birmingham; 3 Antiviral Susceptibility Reference Unit, University of Birmingham, Birmingham; 4 Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
* Corresponding author. Tel: +44-787-678-1398; Fax: +44-1227-783-074; Email: adilisaac{at}yahoo.com
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
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