3 years ago

The impact of diuretic use and ABCG2 genotype on the predictive performance of a published allopurinol dosing tool

Jill Drake, Daniel F.B. Wright, Lisa K. Stamp, Anne Horne, Murray L. Barclay, Tony R. Merriman, Paul Tan, Amanda J. Phipps-Green, Nicola Dalbeth
This research aims to evaluate the predictive performance of a published allopurinol dosing tool. Allopurinol dose predictions were compared to the actual dose required to achieve serum urate (SU) <0.36 mmol L-1 using mean prediction error. The influence of patient factors on dose predictions was explored using multilinear regression. Allopurinol doses were over-predicted by the dosing tool, however, this was minimal in patients without diuretic therapy (MPE 63mg day-1, 95%CI 40-87) compared to those receiving diuretics (MPE 295mg day-1, 95%CI 260-330, p<0.0001). ABCG2 genotype (rs2231142, G>T) had an important impact on the dose predictions (MPE 201, 107, 15mg day-1 for GG, GT and TT, respectively, p<0.0001). Diuretic use and ABCG2 genotype explained 53% if the variability in prediction error (R2=0.53, p=0.0004). The dosing tool produced acceptable maintenance dose predictions for patients not taking diuretics. Inclusion of ABCG2 genotype and a revised adjustment for diuretics would further improve the performance of the dosing tool.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bcp.13516

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