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Predicting allopurinol response in patients with gout
Author(s) -
Wright Daniel F. B.,
Duffull Stephen B.,
Merriman Tony R.,
Dalbeth Nicola,
Barclay Murray L.,
Stamp Lisa K.
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12799
Subject(s) - allopurinol , gout , nonmem , medicine , diuretic , renal function , body weight , pharmacokinetics , population , uric acid , pharmacology , plasma concentration , urology , endocrinology , environmental health
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.