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 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.
Gwilt
Peter R
PR
College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Manouilov
Konstantine K
KK
McNabb
JoCarol
J
Swindells
Susan S
SS
D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy; D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D008875:Middle Aged
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D006918:Hydroxyurea