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

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.