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Effect of age and gender on tirilazad pharmacokinetics in humans
Author(s) -
Hulst Laura K,
Fleishaker Joseph C,
Peters Gary R,
Harry John D,
Wright D Mark,
Ward Penelope
Publication year - 1994
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1994.45
Subject(s) - pharmacokinetics , medicine , plasma clearance , clearance rate , anesthesia , dosing , pharmacology
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. The 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. Clinical Pharmacology and Therapeutics (1994) 55, 378–384; doi: 10.1038/clpt.1994.45