diphenyl - dimethyl - dicarboxylate ( pmc : nissel , taerim pharma co. , korea ) , a hepatotonic drug , is a substance derived from the synthesis of schizandrae fructus elements . although this drug is used in clinical medicine , its action and interactions with other drugs have not been elucidated . we have encountered two cases of drug interaction between csa ( sandimmun , sandoz pharmaceuticals , basle ) and pmc in kidney transplants with chronic hepatitis . both cases showed a reduction of csa trough to a subtherapeutic level following pmc treatment . two months following transplantation , serum transaminases showed a persistent elevation . viral markers tested at 17 months after transplantation were hbsag / sab / cab ( /+/+ ) , anti - hcv(+ ) and cmv ab igg / igm ( + / ) . thirty months following transplantation , pmc ( 75mg / day , each tablet contains 25 mg of pmc ) was given orally for 6 successive weeks . laboratory tests on starting pmc treatment indicated a csa trough level of 97.7ng / ml ( by monoclonal antibody radioimmunoassay , whole blood ) and a serum creatinine level of 1.8mg / dl . alanine transferase ( alt ) measured 2 weeks before pmc therapy was 71iu / l . the csa trough level fell to 78.0ng / ml after 4 weeks and 49.0ng / ml after 6 weeks of pmc treatment , and no drugs were added or withdrawn . upon cessation of pmc treatment , the csa trough rose gradually , reaching 106.6mg / ml after 4 weeks and 137.4ng / ml after 8 weeks ( fig . a 53-year - old male kidney transplant showed intermittent elevations in transaminases 1 month after transplantation . viral markers tested at 36 months following transplantation were hbsag / sab / cab ( //+ ) , anti - hcv ( + ) and cmv ab igg / igm ( + /+ ) . thirty - six months after transplantation , pmc ( 75mg / day ) was given orally for 17 successive weeks . laboratory tests on starting pmc treatment indicated csa trough level of 127.5ng / ml , an alt of 130 iu / l and a serum creatinine of 1.8mg / dl . the csa trough level fell to 70.5 and 45.0ng / ml after 8 and 16 weeks of pmc therapy , respectively , despite the same dose of csa being given . at the second week of pmc treatment , the dose of prednisolone seven weeks after discontinuation of pmc treatment , the csa trough rose 73.3ng / ml and , 12 weeks after , it reached 120.0ng / ml ( fig . two months following transplantation , serum transaminases showed a persistent elevation . viral markers tested at 17 months after transplantation were hbsag / sab / cab ( /+/+ ) , anti - hcv(+ ) and cmv ab igg / igm ( + / ) . thirty months following transplantation , pmc ( 75mg / day , each tablet contains 25 mg of pmc ) was given orally for 6 successive weeks . laboratory tests on starting pmc treatment indicated a csa trough level of 97.7ng / ml ( by monoclonal antibody radioimmunoassay , whole blood ) and a serum creatinine level of 1.8mg / dl . alanine transferase ( alt ) measured 2 weeks before pmc therapy was 71iu / l . the csa trough level fell to 78.0ng / ml after 4 weeks and 49.0ng / ml after 6 weeks of pmc treatment , and no drugs were added or withdrawn . upon cessation of pmc treatment , the csa trough rose gradually , reaching 106.6mg / ml after 4 weeks and 137.4ng / ml after 8 weeks ( fig . a 53-year - old male kidney transplant showed intermittent elevations in transaminases 1 month after transplantation . viral markers tested at 36 months following transplantation were hbsag / sab / cab ( //+ ) , anti - hcv ( + ) and cmv ab igg / igm ( + /+ ) . thirty - six months after transplantation , pmc ( 75mg / day ) was given orally for 17 successive weeks . laboratory tests on starting pmc treatment indicated csa trough level of 127.5ng / ml , an alt of 130 iu / l and a serum creatinine of 1.8mg / dl . the csa trough level fell to 70.5 and 45.0ng / ml after 8 and 16 weeks of pmc therapy , respectively , despite the same dose of csa being given . at the second week of pmc treatment , the dose of prednisolone seven weeks after discontinuation of pmc treatment , the csa trough rose 73.3ng / ml and , 12 weeks after , it reached 120.0ng / ml ( fig . the vast majority of the drugs that interact with csa cause either an increase or decrease in csa blood level , thereby exposing the patient to the risk of development of renal dysfunction associated with a high csa level , or graft rejection due to a subtherapeutic level . these effects are primarily attributed to the inhibition or induction of the p-450 microsomal enzyme system which metabolizes csa . induction of the p-450 microsomal enzyme system by drugs such as phenytoin , phenobarbital , carbamazepine and rifampin may significantly decrease the blood concentration of csa . pmc has been suggested to be effective in treating toxic hepatitis induced by cci4 in animal model and in chronic hepatitis in humans . although pmc is clinically used , the mechanism of action and its interaction with other drugs have not been identified . we experienced two cases of drug interaction between csa and pmc in kidney transplants with chronic hepatitis . the duration of pmc therapy was 6 weeks in one case and 17 weeks in the other . in both cases , however , the dose of csa was not increased becaues of the possibility of csa hepatotoxicity . no drugs influencing the csa trough level , the dose of oral prednisolone was decreased from 5 to 2.5mg / day on the second week of pmc treatment . this , however , might not alter the interaction between csa and pmc , as the csa level readily reverted to the control level after the cessation of pmc treatment . although no episode of acute rejection was observed in the present study , some risks of acute rejection due to reduced csa level may be considered in pmc therapy in humans . to identify the mechanism of interaction between pmc and csa , analysis of the p-450 microsomal enzyme activity and the csa metabolites in animal model may be required .
an adequate blood level of cyclosporine - a ( csa ) is essential to keep graft function in kidney transplants . due to a narrow therapeutic index and highly variable pharmacokinetic properties associated with csa 
 , drug interactions may have a significant impact on the immunosuppressive efficacy or toxicity of csa . 
 numerous drug interactions of potential clinical significance involving csa have been reported.diphenyl-dimethyl-dicarboxylate ( pmc ) , a hepatotonic drug , is a substance derived from the synthesis of schizandrae fructus elements . 
 we have experienced two cases of drug interaction between csa and pmc in kidney transplants with chronic hepatitis . in both cases , 
 csa troughs decreased markedly to a subtherapeutic level following administration of pmc.we , therefore , suggest that pmc could decrease the csa trough level and thus a dose monitoring of the csa trough level is necessary during a pmc therapy .