RELATIVE POTENCY BETWEEN CYCLOSPORINE AND TACROLIMUS EVALUATED FROM LYMPHOCYTE SUPPRESSION TEST IN VITRO AND CLINICAL PHARMACOKINETICS PARAMETER

Abstract

A232 Aims: We evaluated clinical relative potency between cyclosporine(CYA) and tacrolimus(TAC) with point of view of pharmacodynamics and pharmacokinetics to find out the most suitable converting dose between both drugs. Methods: The relative pharmacodynamics potency between CYA and TAC was examined for reciprocal of mean ratio of concentrations of CYA and TAC that gave 50% inhibition of in vitro blastogenesis of mitogen-stimulated lymphocyte(IC50) obtained 66 chronic renal failure(CRF) patients waiting renal transplantation. The relative potency estimated from clinical pharmacokinetics parameters was examined for reciprocal of mean ratio of each pharmacokinetics parameter values between CYA and TAC. The area under the concentration-time curve(AUC), the trough level(Cmin), the peak level(Cmax) and their parameter values divided by dose per body weight dose as pharmacokinetics parameter were measured by 12-hours monitoring of blood concentrations on 7 patients administrated CYA microemulsion formulation and 7 patient administrated TAC in one month after renal transplant operation. Results: The mean ratio of IC50 between CYA and TAC(CYA/TAC of IC50) was 25.1. The mean ratio of AUC(CYA/TAC of AUC) was 25.5, the mean ratio of Cmin(CYA/TAC of Cmin) was 13.2, and the mean ratio of Cmax(CYA/TAC of Cmax) was 38.0. The mean ratio of dose per body weight(CYA/TAC of dose/weight) was 25.2. Further their each mean pharmacokinetics parameter ratio values(CYA/TAC of AUC, CYA/TAC of Cmin, and CYA/TAC of Cmax) divided by dose per body weight were 0.95, 0.49, and 1.44 respectively. Conclusions: It is usually thought that AUC of calcineurin inhibitor is pharmacokinetics parameters being related to the most clinical efficacy. The relative potency that estimated from the AUC between CYA and TAC was almost equal to the relative pharmacodynamics potency estimated from IC50, further CYA/TAC of dose/weight also. Therefore we concluded that the potency of TAC was 25-fold superior to CYA and the relative potency value could useful to convert between both drugs. CYA/TAC of AUC divided by dose per body weight was 0.95, namely the bioavailability of both drugs was almost same. CYA/TAC of Cmin was less than CYA/TAC of AUC, oppositely CYA/TAC of Cmax was more, as CYA had higher peak level and lower trough level than TAC, though the both drug had the same bioavailability. For it was thought that CYA/TAC of Cmin and CYA/TAC of Cmax could not reveal actually relative potency.