The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout

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Abstract
Summary The objectives of this study were to establish if, and to what extent, benzbromarone affects allopurinol/oxypurinol kinetics, and to compare the uric acid lowering capabilities of Allomaron® (allopurinol 100 mg plus benzbromarone 20 mg) with the effects of allopurinol alone in patients with confirmed gout. We studied 14 adult men in an open randomized cross-over study. After a 14 day run-in period with Zyloprim® (2×100 mg allopurinol tablets in the morning), the patients were randomly allocated to morning doses of either Allomaron® (2 tablets) or Zyloprim® (2 tablets). Seven days later cross-over was effected and the alternative treatment was taken for a further 7 days. On days 7 and 14 the patients came into hospital and venous blood samples were taken over 24 h for allopurinol and oxypurinol assays by HPLC. Serum uric acid was determined on days -14, 1, 7, and 14. Benzbromarone lowered plasma oxypurinol concentrations (Allomaron®/Zyloprim® mean ratio of AUC0→24 was 59%; 95% confidence interval 54–64%), but did not affect plasma allopurinol concentrations. Despite this pharmacokinetic interaction of benzbromarone with allopurinol, resulting in lower plasma concentrations of oxypurinol, Allomaron® was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone.