Document Detail


Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis.
MedLine Citation:
PMID:  17721097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
24552417 - Pharmacogenomics in dermatology: taking patient treatment to the next level.
12616617 - Effect of oxymetholone on sce frequency in human lymphocyte chromosomes in vitro.
24063887 - Drug-induced aseptic meningitis secondary to trimethoprim/sulfamethoxazole: a headache ...
22990077 - Clostridium difficile colitis: review of the therapeutic approach.
10613927 - Modeling of drug release from swellable polymers.
8623717 - Endocarditis in injection drug users.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  AIDS (London, England)     Volume:  21     ISSN:  0269-9370     ISO Abbreviation:  AIDS     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-27     Completed Date:  2007-11-08     Revised Date:  2014-02-06    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  1899-907     Citation Subset:  IM; X    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenine / administration & dosage,  analogs & derivatives,  blood,  pharmacokinetics
Administration, Oral
Adult
Anti-Retroviral Agents / administration & dosage*,  blood,  pharmacokinetics
Benzoxazines / administration & dosage,  blood,  pharmacokinetics
Deoxycytidine / administration & dosage,  analogs & derivatives,  blood,  pharmacokinetics
Drug Therapy, Combination
Female
Genitalia, Female / metabolism*
HIV Infections / blood,  drug therapy*
HIV Protease Inhibitors / administration & dosage,  blood,  pharmacokinetics
Humans
Lamivudine / administration & dosage,  blood,  pharmacokinetics
Lopinavir
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
Grant Support
ID/Acronym/Agency:
AI50410/AI/NIAID NIH HHS; AI54980/AI/NIAID NIH HHS; 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
Chemical
Reg. No./Substance:
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
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Long-term effects of intermittent interleukin-2 therapy in chronic HIV-infected patients (ANRS 048-0...
Next Document:  Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: res...