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- Title
The impact of diuretic use and <italic>ABCG2</italic> genotype on the predictive performance of a published allopurinol dosing tool.
- Authors
Wright, Daniel F. B.; Dalbeth, Nicola; Phipps‐Green, Amanda J.; Merriman, Tony R.; Barclay, Murray L.; Drake, Jill; Tan, Paul; Horne, Anne; Stamp, Lisa K.
- Abstract
Aim: This research aims to evaluate the predictive performance of a published allopurinol dosing tool. Methods: 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. Results: Allopurinol doses were overpredicted by the dosing tool; however, this was minimal in patients without diuretic therapy (MPE 63 mg day−1, 95% CI 40–87) compared to those receiving diuretics (MPE 295 mg 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, 15 mg day−1 for GG, GT and TT, respectively, P < 0.0001). Diuretic use and ABCG2 genotype explained 53% of the variability in prediction error (R2 = 0.53, P = 0.0004). Conclusions: 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.
- Subjects
PHARMACOKINETICS; DRUG metabolism; HEALTH outcome assessment; GENOTYPES; ALLOPURINOL
- Publication
British Journal of Clinical Pharmacology, 2018, Vol 84, Issue 5, p937
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/bcp.13516