Predicting allopurinol response in patients with gout

AIMS: The primary aim of this research was to predict the allopurinol maintenance doses required to achieve the target plasma urate of ≤0.36 mmol l(-1) . METHODS: A population analysis was conducted in nonmem using oxypurinol and urate plasma concentrations from 133 gout patients. Maintenance dose predictions to achieve the recommended plasma urate target were generated. RESULTS: The urate response was best described by a direct effects model. Renal function, diuretic use and body size were found to be significant covariates. Dose requirements increased approximately 2-fold over a 3-fold range of total body weight and were 1.25-2 fold higher in those taking diuretics. Renal function had only a modest impact on dose requirements. CONCLUSIONS: Contrary to current guidelines, the model predicted that allopurinol dose requirements were determined primarily by differences in body size and diuretic use. A revised guide to the likely allopurinol doses to achieve the target plasma urate concentration is proposed.