Lopinavir/ritonavir combined with twice-daily 400 mg indinavir: pharmacokinetics and pharmacodynamics in blood, CSF and semen
| Autor: | Susan M. Drake, Erasmus Smit, Sarah E. Gibbons, David Back, Patricia A. Cane, Adil Isaac, David White, Saye Khoo, Stephen Taylor |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Microbiology (medical) Lopinavir/ritonavir HIV Infections Indinavir Pyrimidinones Pharmacology Lopinavir Mass Spectrometry Pharmacokinetics Semen immune system diseases Blood plasma medicine Humans Pharmacology (medical) Chromatography High Pressure Liquid business.industry virus diseases HIV Protease Inhibitors Middle Aged Viral Load biochemical phenomena metabolism and nutrition CD4 Lymphocyte Count Drug Combinations Infectious Diseases Blood chemistry Area Under Curve Pharmacodynamics HIV-1 RNA Viral Ritonavir business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 54:498-502 |
| ISSN: | 1460-2091 |
| DOI: | 10.1093/jac/dkh357 |
| Popis: | To evaluate the steady-state blood plasma (BP), CSF and seminal plasma (SP) pharmacokinetics (PK) of twice-daily indinavir 400 mg and lopinavir/ritonavir.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.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 C(max), C(min) and AUC(0-12) increased by 9%, 46% and 20%, respectively (P0.32, P0.32 and P0.20). 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 C(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 (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.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 were80 ng/mL in seven of eight plasma samples, and all CSF and semen samples collected. |
| Databáze: | OpenAIRE |
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