The pharmacokinetics of oxypurinol in people with gout

Sophie L Stocker, Andrew John McLachlan, Radojka M Savic, Carl Michael James Kirkpatrick, Garry G Graham, Kenneth M Williams, Richard O Day

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

AIMS Our aim was to identify and quantify the sources of variability in oxypurinol pharmacokinetics and explore relationships with plasma urate concentrations. METHODS Non-linear mixed effects modelling 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 was 1.8, 0.6, 0.3 and 0.18lh-1, respectively. Model predictions showed a relationship between plasma oxypurinol and urate concentrations and failure to reach target oxypurinol concentrations using suggested allopurinol dosing guidelines. CONCLUSIONS In conclusion, 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 degrees of renal impairment.
Original languageEnglish
Pages (from-to)477 - 489
Number of pages13
JournalBritish Journal of Clinical Pharmacology
Volume74
Issue number3
DOIs
Publication statusPublished - 2012

Cite this