Abstract:
:Pre-exposure prophylaxis (PrEP) strategies utilizing anti-retroviral drugs show considerable promise for HIV prevention. However there is insufficient pharmacokinetic (PK) data on drug concentrations required for protection at the relevant mucosal tissues where the infection is initiated. Here we evaluated the utility of a humanized mouse model to derive PK data on two leading drugs, the RT inhibitor Tenofovir (TFV) and CCR5 inhibitor Maraviroc (MVC). Following oral dosing, both the drugs and the intracellular active TFV-diphosphate could be detected in vaginal, rectal and intestinal tissues. The drug exposures (AUC₂₄ h) were found to be higher in vaginal tissue compared to plasma with even higher levels detected in rectal and intestinal tissues. The overall trends of drug concentrations seen in humanized mice reflect those seen in the human thus establishing the utility of this model complementing the present non-human primate (NHP) models for future pre-clinical evaluations of promising HIV PrEP drug candidates.
journal_name
Virologyjournal_title
Virologyauthors
Veselinovic M,Yang KH,LeCureux J,Sykes C,Remling-Mulder L,Kashuba ADM,Akkina Rdoi
10.1016/j.virol.2014.07.008subject
Has Abstractpub_date
2014-09-01 00:00:00pages
253-263eissn
0042-6822issn
1096-0341pii
S0042-6822(14)00314-6journal_volume
464-465pub_type
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