论文部分内容阅读
Background: Pre-dose concentration measurement is the most practical method to evaluate cyclosporine(CsA) therapy in renal transplant patients. But it gives no information about the total drug exposure,which relate to graft survival. A number of different new concepts of CsA monitoring,including approaches such as single,double,triple time-point and abbreviated area under curve(AUC) determinaiton,have been introduced. The full CsA AUC value is the most sensitive indicator of clinical outcome. However,its higher analytical costs and time-consuming sampling compromise the benefit of full AUC. Alternative method of predicted AUC by using 2 concentration-time points have been established and used for routine practice in our hospital. [Objectives] The purpose of this study is to determine more sensitive and more predictive markers for CsA dosage adjustment in renal transplant patients. [Methods] Total 44 patients completed the 12-hours CsA pharmacokinetic studies. They had stable renal function. None of them had history of gastrectomy,small bowel resection,cholecystectomy,cholestasis,or had use of medications that might cause an interaction with CsA before the study. Pharmacokinetic parameters were evaluated by use of noncompartmental methods. The correlation equations between drug concentration-time points and AUC were determined by simple and multiple linear regression models using one,two,or three concentration time points as independent variable. [Results] Most of Cmax achieved at about 1～2 hours after dosing,but some delayed absorption was observed at abour 3～5 hours after dosing. C0 and C1 are poorly correlated with AUC of CsA,two of three point have better correlation than single point. Depending on clinical outcomes,predicted AUC goes more reliable than single concentration-time point monitoring for consideration of total exposure amount of CsA. If Tmax of CsA concentration-time curve shifted(delayed) out of population range,the AUC prediction error will be increased and give misleading in dose adjustment. [Conclusions] Predicted AUC by C0/C2 equation is the best precise estimator of total CsA exposure in renal transplant patients. Rational basis for dose adjustments and reduce incidence of graft rejection. Pharmacodynamic level is still a problem in transplant patients. Which level of AUC should be taken for our patient to prolong the survival time must be the future work in our unit.