Fig. 4.
Association of OAT1-mediated tenofovir transport efficiency (Vmax/Km) with SUA levels and effect of amino acid substitutions in hOAT1 on tenofovir uptake rate. (A) Mean ± S.D. of SUA levels (black bar) and OAT1-mediated tenofovir transport efficiencies (gray bar) in species with (cynomolgus monkey, squirrel monkey, mouse, rat, and dog) and without (human, chimpanzee, gorilla, orangutan, and gibbon) functional uricase (* represents comparison of SUA levels in species with and without uricase; # represents comparison of tenofovir transport efficiencies in species with and without uricase; **P < 0.01; ####P < 0.0001). (B) [3H]-tenofovir uptake by hOAT1, cyOAT1, and mutants (hOAT1 S203T and hOAT1 S203A). Transiently transfected HEK293 cells overexpressing wild-type or mutant proteins were incubated with [3H]-tenofovir (50 nM) for 3 minutes. Transporter-mediated tenofovir uptake was obtained after subtracting the respective rate of uptake in empty vector cells.