Lacroix C, Guyonnaud C, Chaou M, Duwoos H, Lafont O
Department of Pharmacokinetics, Centre Hospitalier Général, Le Harve, France.
Eur Respir J. 1988 Oct;1(9):807-11.
Pyrazinamide (PZA) is increasingly used with isoniazid and rifampicin, in short-course antituberculous chemotherapy in service programme conditions. Complicating arthralgias occur due to hyperuricaemia induced by the inhibition of renal tubular secretion of uric acid by pyrazinoic acid, the main PZA metabolite. Allopurinol (Al), a hypouricaemic agent, provides no substantial clinical improvement. Pharmacokinetics of PZA and its metabolites were studied in six healthy volunteers, in a cross-over design, after a single oral dose of PZA alone and, in a second trial, after the same dose together with Al. Plasma and urinary concentrations were measured by high pressure liquid chromatography with a column of cation exchange resin. Analysis of the pharmacokinetic parameters showed that Al induced marked changes in levels of PZA metabolites and accumulation of pyrazinoic acid. Despite decreasing uric acid synthesis, allopurinol increased plasma concentrations of pyrazinoic acid, which is directly responsible for the inhibition of renal urate secretion. Other drugs, which do not involve xanthine oxidase inhibition, should be used in the treatment of this side effect of chemotherapy.
吡嗪酰胺（PZA）越来越多地与异烟肼和利福平一起用于服务项目条件下的短程抗结核化疗。由于主要的PZA代谢产物吡嗪酸抑制肾小管尿酸分泌导致高尿酸血症，从而出现关节痛并发症。降尿酸药物别嘌醇（Al）并未带来实质性的临床改善。在一项交叉设计中，对6名健康志愿者进行了研究，在单次口服单独的PZA后，以及在第二项试验中，在口服相同剂量PZA的同时服用Al后，研究了PZA及其代谢产物的药代动力学。通过使用阳离子交换树脂柱的高压液相色谱法测量血浆和尿液浓度。药代动力学参数分析表明，Al引起了PZA代谢产物水平的显著变化以及吡嗪酸的蓄积。尽管别嘌醇减少了尿酸合成，但它增加了直接导致肾尿酸分泌抑制的吡嗪酸的血浆浓度。在治疗化疗的这种副作用时，应使用不涉及黄嘌呤氧化酶抑制的其他药物。
