Pharmacokinetics of hydroxyurea in plasma and cerebrospinal fluid of HIV-1-infected patients

Peter B. Gwilt, Konstantine K. Manouilov, Jo Carol McNabb, Susan S. Swindells

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1003-1007
Number of pages5
JournalJournal of Clinical Pharmacology
Volume43
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Antiretroviral drugs
  • HIV-associated dementia
  • Hydroxyurea
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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