EFFECT OF AGE AND GENDER ON TIRILAZAD PHARMACOKINETICS IN HUMANS

Tirilazad mesylate pharmacokinetics were assessed in 12 young and 12 e lderly volunteers (six men and six women per age group). Subjects rece ived single 10-minute intravenous infusions of 1.5 mg/kg and 3.0 mg/kg tirilazad mesylate. Plasma tirilazad mesylate concentrations were det ermined by HPLC. The were no significant dose effects on clearance, bu t 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 cl earance in elderly volunteers was primarily attributable to a lower cl earance 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 i n young men. The clinical importance of this observation is unknown.