Population Pharmacokinetics and Target Attainment of Allopurinol and Oxypurinol Before, During, and After Cardiac Surgery with Cardiopulmonary Bypass in Neonates with Critical Congenital Heart Disease.

Summary

Population pharmacokinetic study of intravenous allopurinol and its metabolite oxypurinol in 14 neonates with critical congenital heart disease enrolled in the CRUCIAL trial, which is testing allopurinol for neuroprotection around cardiac surgery with cardiopulmonary bypass. It describes how clearance changes with postnatal age and during and after bypass, and evaluates target attainment of the trial dosing strategy. Reduced clearance during bypass was attributed to hypothermia, haemofiltration and circuit sequestration, and reduced oxypurinol clearance afterwards to impaired kidney function. The dosing was judged adequate as concentrations maintained xanthine oxidase inhibition throughout.

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