St Peter J V, Brady M E, Foote E F, Dandekar K A, Smaldone L, Pykkonen J L, Keane W F, Halstenson C E
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN.
Eur J Clin Pharmacol. 1993;45(1):59-63. doi: 10.1007/BF00315351.
We have studied the disposition of batanopride and its three major metabolites (the erythro-alcohol, threo-alcohol, and N-desethyl metabolites) in 27 subjects with various degrees of renal function after intravenous infusion of a single dose of 3.6.mg.kg-1 of batanopride over 15 min. The subjects were assigned to one of three treatment groups: group 1, normal renal function (creatinine clearance > or = 75 ml.min-1 x 1.73 m-2; n = 13); group 2, moderate renal impairment (creatine clearance 30-60 ml.min-1 x 1.73 m-2; n = 8); group 3, severe renal impairment (creatinine clearance < or = 30 ml.min-1 x 1.73 m-2; n = 6). The terminal half-life of batanopride was significantly prolonged from 2.7 h in group 1 to 9.9 h in group 3. The renal clearance of batanopride was significantly lower in group 3 (25 ml.min-1) compared with group 1 (132 ml.min-1). There were no differences in plasma protein binding or steady-state volume of distribution of batanopride among the groups. There were significantly lower renal clearances for all three metabolites in groups 2 and 3 compared with group 1. The half-lives of all three metabolites were significantly prolonged in group 3 compared with group 1. The dose of batanopride may need to be reduced in patients with creatinine clearances less than 30 ml.min-1 x 1.73 m-2 to prevent drug accumulation and avoid possible dose-related adverse effects.
我们研究了27名不同程度肾功能的受试者在静脉输注单剂量3.6mg·kg⁻¹巴他必利15分钟后，巴他必利及其三种主要代谢物（赤藓醇、苏阿糖醇和N-去乙基代谢物）的处置情况。受试者被分为三个治疗组之一：第1组，肾功能正常（肌酐清除率≥75ml·min⁻¹×1.73m⁻²；n = 13）；第2组，中度肾功能损害（肌酐清除率30 - 60ml·min⁻¹×1.73m⁻²；n = 8）；第3组，重度肾功能损害（肌酐清除率≤30ml·min⁻¹×1.73m⁻²；n = 6）。巴他必利的终末半衰期从第1组的2.7小时显著延长至第3组的9.9小时。与第1组（132ml·min⁻¹）相比，第3组中巴他必利的肾清除率显著降低（25ml·min⁻¹）。各组之间巴他必利的血浆蛋白结合率或稳态分布容积无差异。与第1组相比，第2组和第3组中所有三种代谢物的肾清除率均显著降低。与第1组相比，第3组中所有三种代谢物的半衰期均显著延长。对于肌酐清除率低于30ml·min⁻¹×1.73m⁻²的患者，可能需要降低巴他必利的剂量，以防止药物蓄积并避免可能的剂量相关不良反应。
