title: Effect of age and gender on tirilazad pharmacokinetics in humans.
abstract: Tirilazad mesylate pharmacokinetics were assessed in 12 young and 12 elderly volunteers (six men and six women per age group). Subjects received single 10-minute intravenous infusions of 1.5 mg/kg and 3.0 mg/kg tirilazad mesylate. Plasma tirilazad mesylate concentrations were determined by HPLC. There were no significant dose effects on clearance, but half-life increased with dose because of assay insensitivity at the lower dose. Mean half-lives were 16.3 +/- 15.5 and 21.4 +/- 12.6 hours for young and elderly subjects, respectively, at the 3.0 mg/kg dose. At the same dose, mean tirilazad mesylate systemic clearance was 0.630 +/- 0.254 and 0.428 +/- 0.090 L/hr/kg, respectively. The decreased clearance in elderly volunteers was primarily attributable to a lower clearance in elderly women relative to young women. The small effect of age on tirilazad clearance is likely to have minimum clinical impact. Tirilazad clearance was approximately 40% higher in young women than in young men. The clinical importance of this observation is unknown.
authors.affiliation: Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49007.
authors.forename: L K
authors.initials: LK
authors.lastname: Hulst
authors.forename: J C
authors.initials: JC
authors.lastname: Fleishaker
authors.forename: G R
authors.initials: GR
authors.lastname: Peters
authors.forename: J D
authors.initials: JD
authors.lastname: Harry
authors.forename: D M
authors.initials: DM
authors.lastname: Wright
authors.forename: P
authors.initials: P
authors.lastname: Ward
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D011281:Pregnatrienes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012044:Regression Analysis; D012727:Sex Characteristics
chemical_list: D008054:Lipid Peroxides; D011281:Pregnatrienes; C053355:tirilazad