STABILITY OF DEBRISOQUINE (CYP2D6) PHENOTYPE IN LIVER-TRANSPLANT PATIENTS

Liver metabolism may be modified after liver transplantation according to the phenotype of the donor and may be influenced by posttransplant ation complications. The CYP2D6 phenotype was assessed in 13 patients (group I) before and after liver transplantation using debrisoquine. C YP2D6 activity was also assessed in vitro on microsomes from the liver of the recipients and the donors, using dextromethorphan. Twelve pati ents were extensive metabolizers both before and after transplantation . One apparently poor metabolizer was transplanted with the liver of a nother poor metabolizer. The intrinsic clearance of dextromethorphan ( CL(int)) measured on recipient liver microsomes was significantly lowe r than that on donor liver microsomes (p < 0.05). In extensive metabol izers, the debrisoquine metabolic ratio was correlated with CL(int) be fore (r = 0.78, p < 0.05) and after (r = 0.89, p < 0.0005) transplanta tion. Debrisoquine phenotype was measured repeatedly in nine additiona l patients (group II) up to 3 years after liver transplantation. Their phenotype was stable during the follow-up observation, although the v ariations observed may be clinically relevant. Therefore, no change in CYP2D6 phenotype (extensive/poor metabolizer) was observed because of the liver transplantation, and the debrisoquine log metabolic ratio w as largely unaffected by the liver complications observed during the p osttransplantation follow-up observation.