Hulst L K, Fleishaker J C, Peters G R, Harry J D, Wright D M, Ward P
Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49007.
Clin Pharmacol Ther. 1994 Apr;55(4):378-84. doi: 10.1038/clpt.1994.45.
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.
在12名年轻志愿者和12名老年志愿者（每个年龄组6名男性和6名女性）中评估了甲磺替拉扎德的药代动力学。受试者接受了1.5mg/kg和3.0mg/kg甲磺替拉扎德单次10分钟的静脉输注。通过高效液相色谱法测定血浆中甲磺替拉扎德的浓度。清除率没有显著的剂量效应，但由于低剂量时检测不敏感，半衰期随剂量增加。在3.0mg/kg剂量下，年轻受试者和老年受试者的平均半衰期分别为16.3±15.5小时和21.4±12.6小时。在相同剂量下，甲磺替拉扎德的平均全身清除率分别为0.630±0.254和0.428±0.090L/小时/千克。老年志愿者清除率降低主要归因于老年女性相对于年轻女性清除率较低。年龄对替拉扎德清除率的微小影响可能对临床影响最小。年轻女性的替拉扎德清除率比年轻男性高约40%。这一观察结果的临床重要性尚不清楚。
