Fanelli G M, Weiner I M
J Pharmacol Exp Ther. 1979 Aug;210(2):186-95.
A derivative of probenecid, 2-nitroprobenecid, was studied in chimpanzees and Cebus monkeys. The uricosuria induced by the drug could be diminished by the infusion of p-aminohippurate (chimpanzee) or hippurate (monkey). Both hippurates inhibited the secretion of the drug and it is likely that the diminished response was the result of decreased access of 2-nitroprobenecid to its site of action. In contrast, pyrazinoate diminished the response to 2-nitroprobenecid without disturbing its renal disposition (both species). This action of pyrazinoate is attributed to its ability to inhibit the secretory flux of urate. The effect of pyrazinoate is diminished at high levels of 2-nitroprobenecid, i.e., it appears as if pyrazinoate causes a shift to the right of the concentration-response curve of 2-nitroprobenecid. A mathematical model is developed which seems to explain this apparent shift in the concentration-response curve. This model requires that the transepithelial fluxes for urate be very large. In the chimpanzee the action of salicylate resembles that of pyrazinoate but it is less prominent.
对丙磺舒的衍生物2-硝基丙磺舒在黑猩猩和卷尾猴身上进行了研究。通过输注对氨基马尿酸（黑猩猩）或马尿酸（猴子），可减少该药物诱导的尿酸尿。两种马尿酸盐均抑制该药物的分泌，反应减弱可能是由于2-硝基丙磺舒到达其作用部位的机会减少所致。相比之下，吡嗪酸盐可减弱对2-硝基丙磺舒的反应，而不影响其在肾脏的处置（两种动物均如此）。吡嗪酸盐的这种作用归因于其抑制尿酸分泌通量的能力。在高剂量的2-硝基丙磺舒时，吡嗪酸盐的作用减弱，也就是说，似乎吡嗪酸盐使2-硝基丙磺舒的浓度-反应曲线向右移动。建立了一个数学模型，该模型似乎可以解释浓度-反应曲线的这种明显移动。该模型要求尿酸的跨上皮通量非常大。在黑猩猩中，水杨酸盐的作用与吡嗪酸盐相似，但不太明显。
