A preliminary pharmacokinetic study of cyclosporine A in 10 Japanese renal transplant patients.

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.