title: NXY-059 does not significantly interact with furosemide in healthy volunteers.
abstract: 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.
authors.affiliation: AstraZeneca R&D, Södertälje, SE-151 85, Södertälje, Sweden. stig.strid@astrazeneca.com
authors.forename: Stig
authors.initials: S
authors.lastname: Strid
authors.forename: Dag
authors.initials: D
authors.lastname: Nilsson
authors.forename: Olof
authors.initials: O
authors.lastname: Borgå
authors.forename: Johan
authors.initials: J
authors.lastname: Wemer
authors.forename: Anders
authors.initials: A
authors.lastname: Grahnén
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001416:Back Pain / Q000139:chemically induced; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D008881:Migraine Disorders / Q000139:chemically induced; D016055:Urinary Retention / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
chemical_list: D001557:Benzenesulfonates; D002317:Cardiovascular Agents; D004232:Diuretics; D005665:Furosemide; C120851:disufenton sodium