Pharmacokinetics of Hydroxyurea in Plasma and Cerebrospinal Fluid of HIV-1-Infected Patients

Hydroxyurea has been shown to potentiate the activity of the antiretroviral nucleoside analogs. A significant complication of AIDS is invasion of the virus into the CNS, resulting in HIV‐associated dementia (HAD). Because of the polar nature of these nucleosides and the presence of efflux pumps in t...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2003-09, Vol.43 (9), p.1003-1007
Main Authors: Gwilt, Peter R., Manouilov, Konstantine K., McNabb, JoCarol, Swindells, Susan S.
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
AIDS Dementia Complex - blood
AIDS Dementia Complex - cerebrospinal fluid
AIDS Dementia Complex - drug therapy
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - blood
Anti-HIV Agents - cerebrospinal fluid
Anti-Retroviral Agents - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
antiretroviral drugs
Antiviral agents
Biological and medical sciences
Chromatography, High Pressure Liquid
Drug Synergism
HIV Infections - blood
HIV Infections - cerebrospinal fluid
HIV Infections - drug therapy
HIV-1
HIV-associated dementia
Human immunodeficiency virus
Humans
Hydroxyurea
Hydroxyurea - administration & dosage
Hydroxyurea - blood
Hydroxyurea - cerebrospinal fluid
Medical sciences
Middle Aged
pharmacokinetics
Pharmacology. Drug treatments
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Summary:Hydroxyurea has been shown to potentiate the activity of the antiretroviral nucleoside analogs. A significant complication of AIDS is invasion of the virus into the CNS, resulting in HIV‐associated dementia (HAD). Because of the polar nature of these nucleosides and the presence of efflux pumps in the blood‐brain barrier, only low CNS drug concentrations are achieved. Introduction of hydroxyurea into the CNS may therefore increase the antiviral activity of these drugs. This study evaluates the accessibility of hydroxyurea to the CNS following oral drug administration. Twelve HIV patients received 800 mg, 1000 mg, or 1200 mg oral hydroxyurea. Cerebrospinal fluid (CSF) and plasma drug concentrations were measured over 8 hours and simultaneously fitted to a pharmacokinetic model. It was determined that CSF hydroxyurea concentrations, corresponding to those found to increase antiretroviral nucleoside activity in vitro, were achieved.
ISSN:0091-2700
1552-4604
DOI:10.1177/0091270003256144