The pharmacokinetics of oxypurinol in people with gout
British Journal of Clinical Pharmacology,

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.

Methods
  • Non–linear mixed effects modeling was applied to concentration–time data from 155 gouty patients with demographic, medical history and renal transporter genotype information.

Results
  • 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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