Is the monkey an appropriate animal model to examine drug-drug interactions involving renal clearance?
The renal drug-drug interaction between famotidine (an H(2) receptor antagonist) and probenecid has not been reproduced in rats. We have proposed that this is caused by a species difference in the transport activity by human/rat organic anion transporter (OAT) 3 and the expression of organic cation transporter (OCT) 1 in the rodent kidney. Since monkey OATs (mkOATs) exhibit similar transport activities to human orthologs, it is hypothesized that in vivo studies in monkeys will allow a more precise prediction of renal drug-drug interactions in humans. Famotidine and cimetidine were efficiently taken up by mkOAT3-expressing human embryonic kidney cells (Km, 154 and 71 microM, respectively), and their uptake was strongly inhibited by probenecid (Ki, 3.0-5.7 microM). Quantification of mkOCT1 and mkOCT2 mRNAs in the monkey kidney using real-time reverse transcription-polymerase chain reaction revealed their predominant expression in the liver and kidney, respectively. Crossover studies were
