THE PHARMACOKINETICS OF INJECTABLE ALLOPURINOL IN NEWBORNS WITH THE HYPOPLASTIC LEFT-HEART SYNDROME

Objective. The purpose of this investigation was to determine the phar macokinetic disposition of intravenous allopurinol and its metabolite oxypurinol in neonates with the hypoplastic left heart syndrome (HLHS) and to evaluate the subsequent degree of xanthine oxidase inhibition using serum uric acid as a marker. Methods. Pharmacokinetic data were evaluated in 12 stable preoperative neonates with HLHS after a single intravenous allopurinol administration of 5 mg/kg or 10 mg/kg. Pharmac okinetic parameters were determined for elimination half-life, clearan ce, volume of distribution, and mean residence time. Xanthine oxidase inhibition, measured by serum uric acid reduction, was also measured. Results. Pharmacokinetic parameters revealed no statistically signific ant differences between a 5-mg/kg and 10-mg/kg dose of intravenous all opurinol on elimination half-life, clearance, volume of distribution, and mean residence time. Mean serum uric acid levels were significantl y reduced from baseline by 39.99 and 42.94%, respectively, in the 5- a nd 10-mg/kg treatment groups. Discussion. The enzyme xanthine oxidase plays a key biochemical role in the generation of toxic oxygen-derived free radicals during ischemia-reperfusion conditions. Allopurinol and its active metabolite oxypurinol inhibit xanthine oxidase, and signif icantly reduce the conversion of hypoxanthine to xanthine and xanthine to uric acid. Cell injury may be caused by toxic oxygen free radicals produced by ischemia-reperfusion injury such as could occur during th e repair of HLHS under hypothermic total circulatory arrest. We hypoth esize that allopurinol may provide protection from cellular injury in this clinical context.