INTERACTION OF ALLOPURINOL AND HYDROCHLOROTHIAZIDE DURING PROLONGED ORAL-ADMINISTRATION OF BOTH DRUGS IN NORMAL SUBJECTS .2. KINETICS OF ALLOPURINOL, OXIPURINOL, AND HYDROCHLOROTHIAZIDE

The kinetics of allopurinol and drochlorothiazide were investigated in seven healthy male subjects during prolonged coadministration of two drugs. Subjects were maintained on an isoenergetic, purine-free formul a 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 hydrochlorothiaz ide was administered. Plasma concentration-time profiles of allopurino l and its main metabolite oxipurinol were obtained on days 1, 10, and 21; hydrochlorothiazide profiles were assessed on days 21 and 43. In a ddition, 24-h plasma concentrations of oxipurinol were measured repeti tively, and 24 h urine samples were collected for the determination of allopurinol, oxipurinol, and hydrochlorothiazide. For oxipurinol, mea n C-max was not altered on hydrochlorothiazide treatment (13.8 +/- 1.4 mu g/ml and 14.7 +/- 2.6 mu g/ml, respectively); mean AUG(0-24) was 2 59 and 290 mu g h(-1) ml(-1), respectively. The small difference in AU G(0-24) values does not explain the increase in plasma uric acid conce ntration during hydrochlorothiazide treatment, nor do the variations i n allopurinol and hydrochlorothiazide kinetics.