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

To determine intracellular concentrations of indinavir (IDV) and investigate the relationship between plasma and intracellular IDV pharmacokinetics in HIV-infected patients. A pharmacokinetic study of 10 patients receiving IDV plus dual nucleoside analogue therapy. Peripheral blood mononuclear cells...

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Bibliographic Details
Published in:Antiviral therapy 2003-06, Vol.8 (3), p.191-198
Main Authors: HENNESSY, Martina, CLARKE, Susan, HAGGARD, Patrick, BACK, David, BARRY, Michael, SPIERS, J. Paul, MULCAHY, Fiona, KELLEHER, Dermot, MEADON, Emma, MAHER, Bridget, BERGIN, Colm, KHOO, Saye, TJIA, John
Format: Article
Language:English
Subjects:
Adult
Anti-HIV Agents - blood
Anti-HIV Agents - pharmacokinetics
Anti-HIV Agents - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Area Under Curve
Biological and medical sciences
Female
Half-Life
HIV Infections - drug therapy
HIV-1
Humans
Indinavir - blood
Indinavir - pharmacokinetics
Indinavir - therapeutic use
Intracellular Space
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
RNA, Viral - blood
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Summary:To determine intracellular concentrations of indinavir (IDV) and investigate the relationship between plasma and intracellular IDV pharmacokinetics in HIV-infected patients. 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. The mean intracellular IDV area under the curve over 8 h (AUC0-8) was lower than the plasma AUC0-8 (7574 +/- 1003 vs 25060 +/- 4171 ng/ml/h; P
ISSN:1359-6535
2040-2058
DOI:10.1177/135965350300800302