Shinosaki T, Yonetani Y
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Jpn J Pharmacol. 1991 Apr;55(4):461-8. doi: 10.1254/jjp.55.461.
Stimulation of uric acid production by the well-known uricosuric drug probenecid was studied using potassium oxonate-treated rats and eviscerated rats subjected to functional hepatectomy. In oxonate-treated rats, probenecid was hyperuricosuric, increasing the glomerular-filtered amounts of uric acid and causing marked hyperuricemia. This could be completely blocked by combination dosing with allopurinol, an inhibitor of xanthine oxidase. In eviscerated rats subjected to functional hepatectomy, probenecid also increased plasma uric acid and urinary uric acid excretion, but when given together with allopurinol, the increase of plasma uric acid was abolished with a remarkable increase of plasma hypoxanthine and xanthine. When probenecid was given by combination dosing with propranolol, a beta adrenoceptor antagonist, the hyperuricemia was also completely blocked. Thus, probenecid is concluded to stimulate uric acid production, probably via some interaction with endogenous catecholamine, resulting in hyperuricemia in rats, although it is a practical hypouricemic drug in humans.
使用草酸钾处理的大鼠和接受功能性肝切除的去内脏大鼠，研究了著名的促尿酸排泄药物丙磺舒对尿酸生成的刺激作用。在草酸钾处理的大鼠中，丙磺舒具有促尿酸排泄作用，增加了肾小球滤过的尿酸量并导致明显的高尿酸血症。这可以通过与黄嘌呤氧化酶抑制剂别嘌醇联合给药而完全阻断。在接受功能性肝切除的去内脏大鼠中，丙磺舒也增加了血浆尿酸和尿尿酸排泄，但当与别嘌醇一起给药时，血浆尿酸的增加被消除，同时血浆次黄嘌呤和黄嘌呤显著增加。当丙磺舒与β肾上腺素能受体拮抗剂普萘洛尔联合给药时，高尿酸血症也被完全阻断。因此，得出结论，丙磺舒可能通过与内源性儿茶酚胺的某种相互作用刺激尿酸生成，导致大鼠高尿酸血症，尽管它在人类中是一种实用的降尿酸药物。
