Aoyama T, Kotaki H, Iga T
Department of Pharmacy, Faculty of Medicine, University of Tokyo, Japan.
J Pharmacobiodyn. 1990 Oct;13(10):647-52. doi: 10.1248/bpb1978.13.647.
The plasma concentration of methylphenidate (MPD) enantiomers after i.v. and oral administration of 0.5-5 mg/kg dose of racemic MPD was compared in rats. In i.v. administration, there was no dose dependence in the pharmacokinetic parameters of both enantiomers in this dose range. In oral administration, although the elimination rate constant of both enantiomers was relatively constant, the total body clearance of both MPD enantiomers decreased remarkably with increasing dose. The relationship between oral dose and the area under the concentration-time curve (AUC) of the individual MPD enantiomers showed a non-linearity. That is, the AUC of both enantiomers increased dramatically with increasing dose more than 2 mg/kg. The recovery (MPD + the metabolite) in urine for 24 h was 16-18% in the range of the oral doses. These results suggest that the dose-dependent characteristics of the MPD enantiomers may be due to the saturation in the presystemic elimination of the drug.
在大鼠中比较了静脉注射和口服0.5-5mg/kg剂量的消旋哌甲酯（MPD）后其对映体的血浆浓度。静脉注射时，在此剂量范围内两种对映体的药代动力学参数均无剂量依赖性。口服给药时，虽然两种对映体的消除速率常数相对恒定，但随着剂量增加，两种MPD对映体的全身清除率显著降低。口服剂量与各MPD对映体浓度-时间曲线下面积（AUC）之间的关系呈非线性。也就是说，当剂量超过2mg/kg时，两种对映体的AUC随剂量增加而急剧增加。口服剂量范围内，24小时尿液中的回收率（MPD+代谢物）为16-18%。这些结果表明，MPD对映体的剂量依赖性特征可能是由于药物的首过消除饱和所致。
