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RISS 인기검색어
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- 저자 : Kashuba, Angela DM (검색결과 1 건)
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Dumond, Julie B,Yeh, Rosa F,Patterson, Kristine B,Corbett, Amanda H,Jung, Byung Hwa,Rezk, Naser L,Bridges, Arlene S,Stewart, Paul W,Cohen, Myron S,Kashuba, Angela DM Lippincott Williams and Wilkins 2007 AIDS -LONDON- CURRENT SCIENCE THEN RAPID SCIENCE P Vol.21 No.14
OBJECTIVES:: To describe first dose and steady state antiretroviral drug exposure in the female genital tract. DESIGN:: Non-blinded, single center, open-label pharmacokinetic study in HIV-infected women. METHOD:: Twenty-seven women initiating combination antiretroviral therapy underwent comprehensive blood plasma and cervicovaginal fluid sampling for drug concentrations during the first dose of antiretroviral therapy and at steady-state. Drug concentrations were measured by validated HPLC/UV or HPLC-MS/MS methods. Pharmacokinetic parameters were estimated for 11 drugs by non-compartmental analysis. Descriptive statistics and 95% confidence intervals were generated using Intercooled STATA Release 8.0 (Stata Corporation, College Station, Texas, USA). RESULTS:: For all antiretroviral drugs, genital tract concentrations were detected rapidly after the first dose. Drugs were stratified according to the genital tract concentrations achieved relative to blood plasma. Median rank order of highest to lowest genital tract concentrations relative to blood plasma at steady state were: lamivudine (concentrations achieved were 411% greater than blood plasma), emtricitabine (395%), zidovudine (235%) tenofovir (75%), ritonavir (26%), didanosine (21%), atazanavir (18%), lopinavir (8%), abacavir (8%), stavudine (5%), and efavirenz (0.4%). CONCLUSIONS:: This is the first study to comprehensively evaluate antiretroviral drug exposure in the female genital tract. These findings support the use of lamivudine, zidovudine, tenofovir and emtricitabine as excellent pre-exposure/post-exposure prophylaxis (PrEP/PEP) candidates. Atazanavir and lopinavir might be useful agents for these applications due to favorable therapeutic indices, despite lower genital tract concentrations. Agents such as stavudine, abacavir, and efavirenz that achieve genital tract exposures less than 10% of blood plasma are less attractive PrEP/PEP candidates.
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