Evaluation of a pharmacokinetic-pharmacodynamic model for hypouricaemic effects of febuxostat using datasets obtained from real-world patients.
AIM
Febuxostat is an active xanthine oxidase (XO) inhibitor which is widely used in the treatment of hyperuricaemia. We aimed to evaluate the predictive performance of a pharmacokinetic-pharmacodynamic (PK-PD) model of the hypouricaemic effects of febuxostat.


METHODS
Previously, we formulated a PK-PD model for predicting the hypouricaemic effects of febuxostat as a function of baseline serum urate levels, body weight, renal function and drug dose, using datasets reported in preapproval studies. Using an updated model with a sensitivity analysis, we examined the predictive performance of the PK-PD model, using datasets obtained from the medical records of patients who received febuxostat from March 2011 to December 2015 at Tokyo Women's Medical University Hospital. Multivariate regression analysis was performed to explore clinical variables to improve the predictive performance of the model.


RESULTS
A total of 1199 serum urate values were retrieved from 168 patients (age: 60.5 ± 17.7 years; 71.4% male) who were receiving febuxostat as a treatment for hyperuricaemia. There was a significant correlation (r = 0.68; P < 0.01) between the serum urate levels observed and those predicted by the modified PK-PD model. A multivariate regression analysis revealed that the predictive performance of the model could be improved further by considering comorbidities (such as diabetes mellitus), estimated glomerular filtration rate (eGFR) and the coadministration of loop diuretics (r = 0.77, P < 0.01).


CONCLUSIONS
The PK-PD model may be useful for predicting individualized maintenance doses of febuxostat in real-world patients.
['Hirai|Toshinori|T|0000-0002-3898-2068', 'Itoh|Toshimasa|T|', 'Kimura|Toshimi|T|', 'Echizen|Hirotoshi|H|']
D000328:Adult D000368:Aged D001835:Body Weight D015897:Comorbidity D066264:Datasets as Topic D003920:Diabetes Mellitus D004305:Dose-Response Relationship, Drug D000069465:Febuxostat D005260:Female D005919:Glomerular Filtration Rate D006074:Gout Suppressants D006801:Humans D033461:Hyperuricemia D008297:Male D008875:Middle Aged D008954:Models, Biological D049994:Sodium Potassium Chloride Symporter Inhibitors D016896:Treatment Outcome D014527:Uric Acid D014969:Xanthine Oxidase
febuxostat hyperuricaemia chronic kidney disease pharmacometrics