Wright C E, Sisson T L, Ichhpurani A K, Peters G R
Clinical Pharmacokinetics and CNS/Critical Care Units, Pharmacia & Upjohn Company, Kalamazoo, Michigan 49007, USA.
J Clin Pharmacol. 1997 Jun;37(6):520-5. doi: 10.1002/j.1552-4604.1997.tb04330.x.
Pramipexole is a dopamine receptor agonist that has proved effective in the treatment of Parkinson's disease. The pharmacokinetic properties of pramipexole at steady-state concentrations were studied in 16 healthy men and women at four dose levels throughout the range recommended for Parkinson's patients. Plasma and urine samples collected within the four dose intervals were assayed for concentrations of pramipexole, using high-performance liquid chromatography. The total oral clearance for all participants was 419 mL/min. The mean volume of distribution and elimination half-life for all participants was 486 +/- 93.2 L and 12.9 +/- 3.27 hours. Concentrations of pramipexole were proportional to dose, although the drug's pharmacokinetic properties differed between men and women. The area under the concentration-time curve for each dose level was 35% to 43% greater in women, mainly because of a 24% to 27% lower oral clearance. The mean creatinine clearance in men and women was 112 +/- 12.8 mL/ min/1.73 m2 and 80.9 +/- 15.6 mL/min/1.73 m2, respectively. The renal clearance of pramipexole accounts for approximately 80% of oral clearance, and there was a significant correlation between renal and creatinine clearances. The influence of gender could not be distinguished from the influence of age and the resulting reduced creatinine clearance, but the measurement of pharmacokinetic properties produced linear results in both men and women.
普拉克索是一种多巴胺受体激动剂，已被证明对帕金森病的治疗有效。在16名健康男性和女性中，研究了普拉克索在帕金森病患者推荐剂量范围内四个剂量水平的稳态浓度下的药代动力学特性。在四个剂量间隔内收集的血浆和尿液样本，使用高效液相色谱法测定普拉克索的浓度。所有参与者的口服总清除率为419 mL/分钟。所有参与者的平均分布容积和消除半衰期分别为486±93.2 L和12.9±3.27小时。尽管该药物的药代动力学特性在男性和女性之间有所不同，但普拉克索的浓度与剂量成正比。女性每个剂量水平的浓度-时间曲线下面积比男性大35%至43%，主要是因为口服清除率低24%至27%。男性和女性的平均肌酐清除率分别为112±12.8 mL/分钟/1.73 m²和80.9±15.6 mL/分钟/1.73 m²。普拉克索的肾清除率约占口服清除率的80%，肾清除率与肌酐清除率之间存在显著相关性。性别影响无法与年龄影响以及由此导致的肌酐清除率降低区分开来，但药代动力学特性的测量在男性和女性中均产生线性结果。
