Correlation Between The Hepatotoxicity And The Whole Blood Concentration Of Cyclosporine

Objective: To investigate the correlation between the whole blood concentrations of cyclosporine A (CsA) and the occurrence of CsA induced hepatotoxicity in the patients on a CsA based immunosuppression regimen after renal transplantation. And to explore the clinical significance of the single-point target concentration for CsA at 2 hour post dose (C2) in evaluating drug hepatic toxicity following renal transplantation. Method: Enzyme rate determination, enzyme circulation and colorimetric method were used to determine the activity of serum Alamine aminotransferase (ALT) and the content of total Bilirubin(TBiL), total Bile Acid(TBA) in the patients and monoclonal fluorescence polarization immunoassay (FPIA) was used to analyze the whole blood CsA concentrations. Cadaver renal transplant recipients treated with CsA(Neoral(?), CsA micromulsion 6~7mg/kg/d) for the first 3 months following surgical procedures were grouped according to the situations of hepatic function. And the differences of CsA trough levels (Co) and the levels at 2 hours after its oral administration (C2) between the two groups were compared. Results: Of 46 recipients whose hepatic function was good before operation, 16 cases had suffered CsA induced liver lesion. The high level of cyclosporine A especially 2 hours after its oral administration has significant toxic effects on the liver. The clinical syndromes are mainly the incidence rate of abnormal in the activity of serum hepatic enzymes and TBA, TBiL was comparatively high. The results of CsA C0, C2 monitoring showed that the difference was not statistically significantbetween Co levels of the recipients with hepatoxicity group and those without hepatoxicity group, while the difference between C2 levels [(1381.97±518.04) vs (1000.04±274.05)ng/ml]] was significant. The correlation between C2 values and AUCo~4 or AUCo-12 was both more excellent than Co. Conclusion: Monitoring of the whole blood concentration of cyclosporine and liver function indicator in individual patients in early phase after the operation may be helpful to making adjustment of his CsA usage so as to prevent effectively the arising of CsA-hepatoxicity when CsA was used for treatment. C2 as a monitoring tool to a adjust to dosage of CsA is a more sensitive and effective predictor than Co for drug induced hepatoxicity. It is suggested that C2 may serve as a conventional parameter for CsA dosage adjustment in clinical practice.