Takada K, Yoshikawa H, Muranishi S, Nagano S, Fukunishi T
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Int J Clin Pharmacol Ther Toxicol. 1987 Aug;25(8):438-42.
A pharmacokinetic study of cyclosporine A (CyA) was performed in ten Japanese renal transplant patients. The peak blood CyA concentration appeared at about 2.5 h after oral administration of CyA 180-360 mg, and the mean peak CyA concentration was 582 +/- 238 (SD) ng/ml. The apparent clearance was 39.9 +/- 16.9 (SD) ml/min/kg which is almost the same as reported in European transplant patients. The apparent distribution volume was 5.34 +/- 3.05 (SD) l/kg. The wide variations observed both in the apparent clearance and in the apparent distribution volume are ascribed to the wide variation of the area under the curve (AUC). No correlation was found between the oral dose per body weight and peak blood CyA level or AUC in the 10 subjects. However, a linearity was ascertained between blood CyA concentrations and oral CyA doses (250 mg and 500 mg), though in one patient. Especially, in one patient, blood CyA level was under the lower detection limit of our assay method, 50 ng/ml, over 20 h after oral administration of CyA. This study strongly supports the need of the blood monitoring in the CyA therapy after renal transplantation.
对10名日本肾移植患者进行了环孢素A（CyA）的药代动力学研究。口服180 - 360mg CyA后，血药CyA浓度峰值约在2.5小时出现，平均峰值CyA浓度为582±238（标准差）ng/ml。表观清除率为39.9±16.9（标准差）ml/min/kg，这与欧洲移植患者的报道几乎相同。表观分布容积为5.34±3.05（标准差）l/kg。表观清除率和表观分布容积中观察到的广泛差异归因于曲线下面积（AUC）的广泛变化。在这10名受试者中，未发现每体重口服剂量与血药CyA峰值水平或AUC之间存在相关性。然而，尽管仅在1名患者中，但确定了血药CyA浓度与口服CyA剂量（250mg和500mg）之间呈线性关系。特别是，1名患者在口服CyA超过20小时后，血药CyA水平低于我们检测方法的下限50ng/ml。本研究有力地支持了肾移植后CyA治疗中进行血药监测的必要性。
