Effect of hydrochlorothiazide on the pharmacokinetics and pharmacodynamics of febuxostat, a non-purine selective inhibitor of xanthine oxidase.

British Journal of Clinical Pharmacology
Brian GrabowskiC Lademacher

Abstract

Hyperuricaemia and gout frequently coexist with cardiovascular disorders such as hypertension and heart failure. The use of diuretics has been re-established as a first-line treatment for patients with hypertension and the effects of diuretics on serum uric acid may diminish the urate-lowering effects of febuxostat, a novel, potent, non-purine selective inhibitor of xanthine oxidase. Co-administration of febuxostat 80 mg and hydrochlorothiazide 50 mg had no effect on the pharmacokinetics and did not have a clinically significant effect on the pharmacodynamics of febuxostat. Dose adjustment for febuxostat is not necessary when it is administered with hydrochlorothiazide. This study examined the effect of co-administration of febuxostat, an investigational urate lowering therapy, and hydrochlorothiazide on the pharmacokinetics and pharmacodynamics of febuxostat. Healthy subjects (36 healthy men and women) received single doses of febuxostat 80 mg alone and febuxostat 80 mg + hydrochlorothiazide 50 mg, separated by 7 days in an open-label, randomized, crossover fashion. Plasma concentrations of febuxostat and urinary and serum concentrations of uric acid were assessed. Mean febuxostat C(max), AUC((0-t)), AUC((0-infinity)), t(1/2,z...Continue Reading

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Citations

Aug 8, 2012·Therapeutic Advances in Musculoskeletal Disease·Ignacio Garcia-ValladaresLuis R Espinoza
Aug 5, 2011·Drugs & Aging·Lisa K Stamp, Sarah Jordan
Apr 2, 2014·Expert Opinion on Drug Metabolism & Toxicology·Harmanjot K GrewalLuis R Espinoza
May 9, 2014·Expert Opinion on Drug Metabolism & Toxicology·Pascal RichetteThomas Bardin
Mar 5, 2016·Expert Review of Clinical Pharmacology·Sandra P ChinchillaFernando Perez-Ruiz
Apr 14, 2016·Journal of Chromatographic Science·Kareem M YounesEman S Elzanfaly
Mar 24, 2018·Arthritis Research & Therapy·Laura RanieriMariano Andres
May 10, 2020·British Journal of Clinical Pharmacology·Bishoy KamelRichard O Day
May 16, 2017·International Journal of Nephrology·Jianmin RanGancheng Lao
Oct 19, 2016·Clinical Pharmacokinetics·Bishoy KamelRichard O Day
May 26, 2018·Pharmaceuticals·Andreas Jordan, Ursula Gresser
Feb 3, 2011·Current Opinion in Rheumatology

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