The pharmacokinetics of oxypurinol in people with gout
British Journal of Clinical Pharmacology, 04/23/2012
Stocker SL et al. – This first established pharmacokinetic model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopurinol therapy in gouty patients with various degree of renal impairment.
Non–linear mixed effects modeling was applied to concentration–time data from 155 gouty patients with demographic, medical history and renal transporter genotype information.
A one–compartment pharmacokinetic model with first–order absorption best described the oxypurinol concentration–time data.
Renal function and concomitant medicines (diuretics and probenecid), but not transporter genotype, significantly influenced oxypurinol pharmacokinetics and reduced the between–subject variability in the apparent clearance of oxypurinol (CL/Fm) from 65% to 29%. CL/Fm for patients with normal, mild, moderate and severe renal impairment were 1.8, 0.6, 0.3 and 0.18 L/h, respectively.
Model predictions show a relationship between plasma oxypurinol and urate concentrations and failure to reach target oxypurinol concentrations using suggested allopurinol dosing guidelines.
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