optimal immunosuppression after organ transplantation from the view point of CYP3A activity

为探讨活体肝移植（LDLT）后CYP 3A活性与环孢素A（CyA）处置的关系，采用单克隆特异性和多克隆非特异性FPIA法测定了LDLT患者（平均年龄± SE，1.7±1.0）。CyA代谢物（主要是1-羟基代谢物）的血液浓度在术后第1天开始增加，并在术后第4天达到稳态。CYP 3A活性在肝移植术后早期仍能维持，而尿6 B-羟皮质醇/皮质醇比值在肝移植术后早期仍能维持。（6 B-OHF/F）是CYP 3A活性的非侵入性标记物，在LDLT患者中在排斥发作前约1或2天增加2至10倍至其正常水平。结果提示，移植肝CYP 3A在术后早期已具有正常活性，尿6 B-OHF/F比值可作为预测排斥反应发生的指标。

To elucidate relationship between CYP3A activity and disposition of cyclosporin A (CyA) after living donor liver transplantation (LDLT), the blood concentrations of CyA and its metabolites by monoclonal specific and polyclonal non-specific FPIA methods were determined in LDLT patients (mean age ± S.E., 1.7±1.0). Blood concentrations of CyA metabolites (mainly 1-hydroxy metabolite) began to increase at post-operative day-1 and they reached steady-state at postoperative day-4. CYP3A activity could maintain even early period after liver transplantation.On the other hand, the ratio of urinary 6B-hydroxycortisol / cortisol (6B-OHF/F), a noninvasive maker of CYP3A activity, in LDLT patients increased 2 to 10-fold to its normal levels at about 1 or 2 days before episode of rejection.In conclusions, the results suggest that CYP3A in the graft liver already has a normal activity in earliest stage after the operation and the ratio of urinary 6B-OHF/F might utilize to predict episode of rejection.