Evaluation of a thiazide-allopurinol drug interaction

Allopurinol toxicity has been associated with the use of this drug in patients with renal insufficiency, a situation where the half-life of oxipurinol, the major metabolite of allopurinol, is prolonged. Allopurinol toxicity has also been associated with the concomitant use of allopurinol and thiazide diuretics. In the present study, the effect of hydrochlorothiazide administration on the renal clearance and serum half-life of oxipurinol has been studied in eight normal volunteers to determine if thiazides delay the clearance of oxipurinol. Oxipurinol's renal clearance and serum half-life were measured in each volunteer during a control period and again while the volunteer was receiving 50 mg/day hydrochlorothiazide for 1 week. No change in renal oxipurinol clearance (21.1 +/- 5.9 vs. 20.4 +/- 8.7 ml/min) or serum oxipurinol half-life (23.7 +/- 4.2 vs. 23.4 +/- 4.4 hours) was noted with the addition of thiazides. The association previously noted between the use of thiazide diuretics and the development of allopurinol toxicity cannot be explained by alterations in oxipurinol pharmacokinetics.