Interaction of allopurinol and hydrochlorothiazide during prolonged oral administration of both drugs in normal subjects. II. Kinetics of allopurinol, oxipurinol, and hydrochlorothiazide.

J X de Vries, A Voss, A Ittensohn, I Walter-Sack, W Löffler, R Landthaler, N Zöllner
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引用次数: 10

Abstract

The kinetics of allopurinol and hydrochlorothiazide were investigated in seven healthy male subjects during prolonged coadministration of two drugs. Subjects were maintained on an isoenergetic, purine-free formula diet with RNA supplementation for 24 days. Allopurinol (300 mg) was given orally on days 1-24. Hydrochlorothiazide (50 mg daily) was added to days 11-21. On day 43 a single oral dose of 50 mg hydrochlorothiazide was administered. Plasma concentration-time profiles of allopurinol and its main metabolite oxipurinol were obtained on days 1, 10, and 21; hydrochlorothiazide profiles were assessed on days 21 and 43. In addition, 24-h plasma concentrations of oxipurinol were measured repetitively, and 24 h urine samples were collected for the determination of allopurinol, oxipurinol, and hydrochlorothiazide. For oxipurinol, mean Cmax was not altered on hydrochlorothiazide treatment (13.8 +/- 1.4 micrograms/ml and 14.7 +/- 2.6 micrograms/ml, respectively); mean AUC0-24 was 259 and 290 micrograms h-1 ml-1, respectively. The small difference in AUC0-24 values does not explain the increase in plasma uric acid concentration during hydrochlorothiazide treatment, nor do the variations in allopurinol and hydrochlorothiazide kinetics.

正常人长期口服别嘌呤醇和氢氯噻嗪时的相互作用。2别嘌呤醇、氧化嘌呤醇和氢氯噻嗪的动力学。
在7名健康男性受试者中,研究了别嘌呤醇和氢氯噻嗪在两种药物长期联合使用期间的动力学。受试者维持等能、不含嘌呤的配方饮食,并补充RNA 24天。别嘌呤醇(300 mg)于第1-24天口服。第11-21天,添加氢氯噻嗪50 mg / d。第43天给予单次口服50 mg氢氯噻嗪。在第1、10和21天获得别嘌呤醇及其主要代谢物氧化嘌呤醇的血浆浓度-时间曲线;在第21天和第43天评估氢氯噻嗪谱。另外,重复测定24小时血浆氧化嘌呤醇浓度,并收集24小时尿液样本测定别嘌呤醇、氧化嘌呤醇和氢氯噻嗪。对于氧化嘌呤醇,氢氯噻嗪治疗未改变平均Cmax(分别为13.8 +/- 1.4微克/毫升和14.7 +/- 2.6微克/毫升);平均值AUC0-24分别为259和290微克h-1毫升-1。AUC0-24值的微小差异并不能解释氢氯噻嗪治疗期间血浆尿酸浓度的增加,也不能解释别嘌呤醇和氢氯噻嗪动力学的变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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