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

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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.