|Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis.|
|PMID: 17721097 Owner: NLM Status: MEDLINE|
|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.
|Julie B Dumond; Rosa F Yeh; Kristine B Patterson; Amanda H Corbett; Byung Hwa Jung; Naser L Rezk; Arlene S Bridges; Paul W Stewart; Myron S Cohen; Angela D M Kashuba|
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|Type: Journal Article; Research Support, N.I.H., Extramural|
|Title: AIDS (London, England) Volume: 21 ISSN: 0269-9370 ISO Abbreviation: AIDS Publication Date: 2007 Sep|
|Created Date: 2007-08-27 Completed Date: 2007-11-08 Revised Date: 2014-10-10|
Medline Journal Info:
|Nlm Unique ID: 8710219 Medline TA: AIDS Country: England|
|Languages: eng Pagination: 1899-907 Citation Subset: IM; X|
|APA/MLA Format Download EndNote Download BibTex|
administration & dosage,
analogs & derivatives,
Anti-Retroviral Agents / administration & dosage*, blood, pharmacokinetics
Benzoxazines / administration & dosage, blood, pharmacokinetics
Deoxycytidine / administration & dosage, analogs & derivatives, blood, pharmacokinetics
Drug Therapy, Combination
Genitalia, Female / metabolism*
HIV Infections / blood, drug therapy*
HIV Protease Inhibitors / administration & dosage, blood, pharmacokinetics
Lamivudine / administration & dosage, blood, pharmacokinetics
Oligopeptides / administration & dosage, blood, pharmacokinetics
Organophosphonates / administration & dosage, blood, pharmacokinetics
Pyridines / administration & dosage, blood, pharmacokinetics
Pyrimidinones / administration & dosage, blood, pharmacokinetics
Reverse Transcriptase Inhibitors / administration & dosage, blood, pharmacokinetics
Zidovudine / administration & dosage, blood, pharmacokinetics
|AI50410/AI/NIAID NIH HHS; AI54980/AI/NIAID NIH HHS; HD001441/HD/NICHD NIH HHS; K12 HD001441/HD/NICHD NIH HHS; K12 HD001441-07/HD/NICHD NIH HHS; K23 AI054980/AI/NIAID NIH HHS; K23 AI054980-05/AI/NIAID NIH HHS; M01 RR000046/RR/NCRR NIH HHS; M01 RR000046-476338/RR/NCRR NIH HHS; P30 AI050410/AI/NIAID NIH HHS; P30 AI050410-129004/AI/NIAID NIH HHS; RR00046/RR/NCRR NIH HHS|
|0/Anti-Retroviral Agents; 0/Benzoxazines; 0/HIV Protease Inhibitors; 0/Oligopeptides; 0/Organophosphonates; 0/Pyridines; 0/Pyrimidinones; 0/Reverse Transcriptase Inhibitors; 0/emtricitabine; 0W860991D6/Deoxycytidine; 107021-12-5/tenofovir; 2494G1JF75/Lopinavir; 2T8Q726O95/Lamivudine; 4B9XT59T7S/Zidovudine; JAC85A2161/Adenine; JE6H2O27P8/efavirenz; QZU4H47A3S/atazanavir|
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