NXY-059 Does Not Significantly Interact With Furosemide in Healthy Volunteers

• Published in: Journal of clinical pharmacology 2006-12, Vol.46 (12), p.1417-1425
• Main Authors: Strid, Stig, Nilsson, Dag, Borgå, Olof, Wemer, Johan, Grahnén, Anders
• Format: Article
• Language: English
• Subjects: Abdominal Pain - chemically induced; Acute ischemic stroke; Adolescent; Adult; Area Under Curve; Back Pain - chemically induced; Benzenesulfonates - administration & dosage; Benzenesulfonates - adverse effects; Benzenesulfonates - pharmacokinetics; Cardiovascular Agents - administration & dosage; Cardiovascular Agents - adverse effects; Cardiovascular Agents - pharmacokinetics; Cross-Over Studies; Diuretics - administration & dosage; Diuretics - pharmacokinetics; Dosage and administration; Double-Blind Method; Drug Interactions; Drug therapy; FARMACI; Female; Furosemide; Furosemide - administration & dosage; Furosemide - pharmacokinetics; Half-Life; Health aspects; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate - drug effects; Middle Aged; Migraine Disorders - chemically induced; neuroprotectant; Nucleoproteins; NXY-059; pharmacodynamics; pharmacokinetics; PHARMACY; Stroke (Disease); Urinary Retention - chemically induced; Vomiting - chemically induced
• ISSN: 0091-2700; 1552-4604; 1552-4604
• DOI: 10.1177/0091270006293372

NXY‐059 is a free radical—trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. Acute ischemic stroke patients receiving NXY‐059 may also be exposed to diuretics for treatment of heart failure or hypertension. NXY‐059 and furosemide are partly eliminated by active tubular secretion via an organic anion transporter. This double‐blind, randomized, crossover, placebo‐controlled study investigated whether an infusion of NXY‐059 (15 mg/mL) during 12 hours affects the diuretic and saluretic effects of a 30‐mg intravenous bolus dose of furosemide (10 mg/mL) administered after 6 hours' infusion, in 13 male and 11 female healthy subjects. The net increase in urine volume and sodium excretion in the interval of 6 to 12 hours was 4.15 L and 178 mmol/L, respectively, during NXY‐059 treatment (P = .93) and 4.34 L and 190 mmol/L, respectively, during placebo treatment (P = .54). NXY‐059 reduced the renal clearance of furosemide by 19% (P = .019), and furosemide reduced the renal clearance of NXY‐059 by 8% (P = .005). NXY‐059 was well tolerated.