The impact of sex and contraceptive therapy on the plasma and intracellular pharmacokinetics of zidovudine.

TitleThe impact of sex and contraceptive therapy on the plasma and intracellular pharmacokinetics of zidovudine.
Publication TypeJournal Article
Year of Publication2006
AuthorsAweeka FT, Rosenkranz SL, Segal Y, Coombs RW, Bardeguez A, Thevanayagam L, Lizak P, Aberg J, D Watts H
Corporate AuthorsNIAID AIDS Clinical Trials Group
JournalAIDS
Volume20
Issue14
Pagination1833-41
Date Published2006 Sep 11
ISSN0269-9370
KeywordsAdministration, Oral, Adult, Contraceptive Agents, Female, Contraceptives, Oral, Combined, Drug Therapy, Combination, Female, HIV Seropositivity, HIV-1, Humans, Injections, Intramuscular, Male, Medroxyprogesterone Acetate, Mestranol, Middle Aged, Norethindrone, Reverse Transcriptase Inhibitors, RNA, Viral, Sex Factors, Viral Load, Zidovudine
Abstract

OBJECTIVES: Zidovudine remains part of combination antiretroviral therapy. Pharmacological studies rely on quantitation of active triphosphates in peripheral blood mononuclear cells. This study evaluated the impact of female sex and contraceptive therapy on zidovudine plasma and intracellular pharmacokinetics and the impact of contraceptive therapy on HIV viral load.

METHODS: Serial plasma and intracellular zidovudine pharmacokinetics following oral and intravenous dosing were determined in 18 men and 20 women treated with zidovudine. Women could repeat pharmacokinetics assessment following 2 months oral or injectable contraceptive therapy. Zidovudine plasma and intracellular mono-, di- and triphosphate concentrations were determined by liquid chromatography tandem mass spectrometry. Plasma and cervical viral loads were determined preceding and following 2 months of contraceptive therapy in women.

RESULTS: Men exhibited higher area under the concentration versus time curve for intracellular zidovudine and zidovudine-monophosphate following oral and intravenous dosing and higher zidovudine triphosphate following oral dosing. There was no difference between men and women in plasma zidovudine parameters. Furthermore, contraceptive therapy had no effect on zidovudine plasma or intracellular pharmacokinetics or on plasma or cervical HIV-1 RNA levels.

CONCLUSIONS: Using an optimized pharmacokinetic design, this study indicated men exhibit significantly higher zidovudine-monophosphate and zidovudine-triphosphate exposure following zidovudine oral administration, having implications for drug toxicity and overall tolerance of zidovudine therapy. The lack of an effect of contraceptive therapy on zidovudine pharmacokinetics is surprising in light of previous pharmacokinetic studies for drugs eliminated primarily through glucuronidation. Contraceptive therapy had no effect on plasma or cervical viral load, results consistent with previous findings.

DOI10.1097/01.aids.0000244202.18629.36
Alternate JournalAIDS
PubMed ID16954724
Grant ListAI25868 / AI / NIAID NIH HHS / United States
AI27663 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27665 / AI / NIAID NIH HHS / United States
AI34832 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States