Study On Monitoring And Pharmacokinetics Of Domestic Cyclosporin In Recipients During The Stable Stage Following Renal Transplantation

OBJECTIVE:To research pharmacokinetic characteristics of two domestic cyclosporine A (CsA) made by different manufacturers; to evaluate the suitability of the two indices C0 and C2 in predicting rejection and toxicity of CsA in stable stage recipients following renal transplantation.METHODS:Fifteen renal transplant recipients, including 7 treated with Tianke and 8 with Xinsaisiping at return visit in TaiAn Central Hospital from June 2009 to March 2010 were involved in the study. All patients were treated with CsA as basic therapy.1.The blood samples were taken 12 times regularly:before oral administration of CsA,0.25,0.5,0.75,1,2,3,4,5,6,9,12h after administration. The concentrtion of CsA in blood was determined by FPIA. The related pharmacokinetic parameters were calculated by DAS2.0 sofeware according to the blood concentration.2. Routine monitoring data for the stable stage recipients with CsA of C0,C2 and AUC0-12h were analysed in our study in order to explore the differences among the domestic preparations.The linear correlation analysis was taken in C0, C2 values and area under the plasma concentration-time curve(AUC)0-12 respectively for the two preparations.Above all, we tried to find a proper monitoring data which is closely related with the effect and toxicity of CsA.RESULTS:The main pharmacokinetic parameters from the 7 patients treated with Tianke were as follows:C0 were (63.71,219.42,74.24,184.41,106.6,75.08 and 204.01)ng/ml, the average was (132.50±67.65) ng/ml,the correlation coefficients between C0 and AUC0-12 was 0.9312; C2 were (456.42,1037.67,747.03,918.41,1004.72,552.05 and 767.41)ng/ml, the average was (783.39±221.31) ng/ml, the correlation coefficients between C2 and AUC0-12 was 0.8914.AUC(0-∞) were (2326.20,4968.23,3235.15,4502.46,4275.33,3018.78,4515.29) ug/(L·h).T1/2 were 3.30,3.31,4.21,4.08,5.30,6.54,4.26.Tmax were 1,2,1,2,2,1,2.Cmax were (728.34,1037.67,767.38,918.41,1004.72,824.26,767.41) ug/L.The main pharmacokinetic parameters from the8 patients treated with Xinsanxiping were as follows:C0 were (87.48,167.03,84.51,62.41,118.73,34.79,261.0 and 244.08)ng/ml,the average was (132.52±83.78) ng/ml,the Correlation Coefficients between Co and AUC0-12 was 0.9722;C2 were (855.67,940.22,606.4,343.97,599.03,410.95,1005.52 and 1366.67)ng/ml, the average was (766.05±341.03) ng/ml, the Correlation Coefficients between C2 and AUC0-12 was 0.9152.AUC(0-∞) were (3282.49,4030.11,2609.18,1873.35,4076.34,2001.50,6774.71,6804.36) ug/(L·h).T1/2 were3.92,3.66,3.81,3.87,6.01,2.90,5.24,4.54.Tmax were 2,2,2,2,1,2,1,2.Cmax were (855.67,940.22,606.4,343.97,1074.02,410.95,1017.25,1366.67) ug/L.CONCLUSIONS:Results suggested that there was great significance in correlationship between C0,C2 and AUC0-12 in the two preparations, Xinsaisiping and Tianke, while C0 was better related to AUC than C2. For the domestic preparations, it was not completely suitable for C2 as the only index for the renal transplantation recipients because of the preparation and human species. C0 is a suitable index for stable stage recipients treated with CsA.Because of the small sample size, C0 as monitor index for stable stage recipients with CsA need to be further verified.