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  • Title: A population pharmacokinetic model to predict oxypurinol exposure in patients on haemodialysis.
    Author: Wright DF, Doogue MP, Barclay ML, Chapman PT, Cross NB, Irvine JH, Stamp LK.
    Journal: Eur J Clin Pharmacol; 2017 Jan; 73(1):71-78. PubMed ID: 27683090.
    Abstract:
    PURPOSE: The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. METHODS: Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not receiving dialysis were used to develop a population pharmacokinetic model in NONMEM. Deterministic simulations were used to predict the steady-state area under the oxypurinol plasma concentration time curve over 1 week (AUC7days). RESULTS: The pharmacokinetics of oxypurinol were best described by a one-compartment model with a separate parameter for dialytic clearance. Allopurinol 100 mg daily produced an AUC7days of 279 μmol/L h in dialysis patients, a value 50-75 % lower than the AUC7days predicted for patients with normal renal function taking 200 to 400 mg daily (427-855 μmol/L h). Dosing pre-dialysis resulted in about a 25-35 % reduction in exposure compared to post-dialysis. CONCLUSIONS: Oxypurinol is efficiently removed by dialysis. The population dialytic and total (non-dialytic) clearance of oxypurinol were found to be 8.23 and 1.23 L/h, standardised to a fat-free mass of 70 kg and creatinine clearance of 6 L/h, respectively. Our results suggest that if the combination of low-dose allopurinol and haemodialysis does not result in sustained urate lowering below treatment targets (serum urate ≤0.36 mmol/L), then allopurinol doses may be increased to optimise oxypurinol exposure.
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