Furosemide increases plasma oxypurinol without lowering serum urate—a complex drug interaction: implications for clinical practice

• Published in: Rheumatology (Oxford, England) Vol. 51; no. 9; pp. 1670 - 1676
• Main Authors: STAMP, Lisa K, BARCLAY, Murray L, O'DONNELL, John L, MEI ZHANG, DRAKE, Jill, FRAMPTON, Christopher, CHAPMAN, Peter T
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2012
• Subjects: Adult; Aged; Allopurinol - pharmacokinetics; Allopurinol - therapeutic use; Area Under Curve; Biological and medical sciences; Case-Control Studies; Diseases of the osteoarticular system; Diuretics - pharmacokinetics; Diuretics - therapeutic use; Drug Interactions; Drug Therapy, Combination; Female; Furosemide - pharmacokinetics; Furosemide - therapeutic use; Gout - drug therapy; Gout - metabolism; Gout Suppressants - pharmacokinetics; Gout Suppressants - therapeutic use; Humans; Inflammatory joint diseases; Male; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Other metabolic disorders; Oxypurinol - blood; Purines and pyrimidines (gout, hyperuricemia...); Treatment Outcome; Uric Acid - blood; Urination - drug effects; Hypouricemic agent; Allopurinol; Gout; Diseases of the osteoarticular system; Rheumatology; Metabolic diseases; Uric acid; oxypurinol; serum urate; Microcristalline arthropathy; Furosemide; Blood plasma; Diuretic; Hyperuricemia; Antihypertensive agent; Serum; Drug interaction; Purine; Microcrystal
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kes091

To determine the effects of furosemide on serum urate (SU), plasma oxypurinol and urinary urate. Twenty-three cases with gout receiving furosemide and allopurinol were recruited. Twenty-three controls with gout receiving allopurinol but no diuretics were matched on age, gender, estimated glomerular filtration rate and allopurinol dose. SU, plasma oxypurinol and urinary urate were assessed on a single occasion. The effects of a single dose of furosemide 40 mg were examined in a separate group of 10 patients receiving allopurinol but not diuretic. Cases had significantly higher SU and plasma oxypurinol compared with controls despite receiving similar doses of allopurinol. There was no difference in urinary urate excretion. There was a significant increase in area under the curve (AUC)(0-24) for oxypurinol after administration of furosemide 40 mg. The interaction between allopurinol and furosemide results in increased SU and plasma oxypurinol. The exact mechanisms remain unclear but complex interactions that result in attenuation of the hypouricaemic effects of oxypurinol are likely. Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, 12609000529246.