한국인 신이식환자에서 Cyclosporin A 의 약리역동학적 연구 = Pharmacokinetics of Cyclosporin A in Korean Renal Transplant Recipients

다국어 초록 (Multilingual Abstract)

The pharmacokinetic monitoring of cyclosporin A (CsA) was performed in Korean renal transplant recipients in order to establish the optimal therapeutic regimen of cyclosporin A in Korean. 1) The pharmacokinetic parameters of CsA were calculated as follows: Volume of distribution(Vd) was 320.5±19.2 L. Clearance(C1) was 1.2±0.1 L/min, Area Under Curve(AUC) was 22733.8±3177.5ngh/ ml. The time of reaching a maximum concentration was about 2 hour and maximum serum concentration was variable between 517.9 and 1909.8ng/mt Pharmacokinetic values after multiple oral dosing with CsA were as follows: The time of reaching a maximum concentration was about 2 hour. Maximum serum concentration was variable between 1850.7 and 4351.7ng/ml. Vd was 201.3±28.9 L. Cl was 0.75k0.09 L/min. AUC was 27563.9±5240.2ngh/ml. 2) During simultaneous administration of isoniazide and rifampin with CsA, the serum concentrations of CsA dropped below the therapeutic level, as much as 9-25% of those of control. The pharmacokinetic calculation in these subjects revealed increased volume of distribution and increased clearance. 3) Successful renal function was achieved without specific complications during upto 6 month follow-up period with the new regimen in which 10 mg cyclosporin A/kg/day was loaded initially for 2 weeks and tapered off to 3mg/kg/day within 2-3 months after renal transplantation, Therefore it is concluded that small Vd, early peak concentration, and slow clearance of CsA, which might be due to the small body fat proportion and genetic difference in hepatic microsomal enzyme system, could reduce the CsA requirement and make the regimen of low does CsA with low does PDL possible and ideal in Korean renal tranaplant recipients and also speculated that RFP and INH induced increment of hepatic metabolic amount might cause the reduction of the serum level of CsA.