Effect of age and gender on tirilazad pharmacokinetics in humans

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.