[Comparative study of the bioavailability and the pharmacodynamic effect of five allopurinol preparations (author's...

The aim of this study was to determine the relative bioavailability of five oral allopurinol preparations and evaluation of the pharmacodynamic effect. Included were two slow-release formulations. The study was performed as complete five-way randomized steady-state cross-over trial in 10 healthy volunteers. Each day 300 mg of 1H-pyrazolo-(3,4-d) pyrimidin-4-ol (allopurinol) were orally administered for 7 days, followed by a wash-out phase of 14 days. The minimal serum levels of allopurinol and its major metabolite oxypurinol were determined by HPLC. In parallel the concentrations of uric acid in blood and in 24-h urine were measured. The two slow-release formulations had a significantly lower relative bioavailability compared to the normal formulations and, moreover, a slow-release effect could not be demonstrated. In all cases the clinical effect of the test preparations could be demonstrated, and a correlation between bioavailability and pharmacodynamic effect could be calculated. A correlation between published in vitro data and the present in vivo data could not be found.