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

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

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

Francesca T Aweeka,Susan L Rosenkranz,Yoninah Segal,Robert W Coombs,Arlene Bardeguez,Lourdes Thevanayagam,Patricia Lizak,Judith Aberg,D Heather Watts, ,

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.

The impact of sex and contraceptive therapy on the plasma and intracellular pharmacokinetics of zidovudine. Publishing Authors By Initials

FT Aweeka,SL Rosenkranz,Y Segal,RW Coombs,A Bardeguez,L Thevanayagam,P Lizak,J Aberg,DH Watts, ,

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

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: AIDS (London, England)

VOLUME: 20

Page Numbers: 1833-41

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ISSN: 0269-9370

DAY: 11

MONTH: Sep

YEAR: 2006

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

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LANGUAGE: eng

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AFFILIATION: Drug Research Unit, University of California, San Francisco, California 94143-0622, USA. faweeka@sfghsom.ucsf.edu

Country: England

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MEDLINETA: AIDS

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