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 posttransplantation complications. The CYP2D6 phenotype was assessed in 13 patients (group I) before and after liver transplantation using debrisoquine. CYP2D6 activity was also assessed in vitro on microsomes from the liver of the recipients and the donors, using dextromethorphan. Twelve patients were extensive metabolizers both before and after transplantation. One apparently poor metabolizer was transplanted with the liver of another poor metabolizer. The intrinsic clearance of dextromethorphan (CL(int)) measured on recipient liver microsomes was significantly lower than that on donor liver microsomes (p < 0.05). In extensive metabolizers, the debrisoquine metabolic ratio was correlated with CL(int) before (r = 0.78, p < 0.05) and after (r = 0.89, p < 0.0005) transplantation. Debrisoquine phenotype was measured repeatedly in nine additional patients (group II) up to 3 years after liver transplantation. Their phenotype was stable during the follow-up observation, although the variations 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 was largely unaffected by the liver complications observed during the posttransplantation follow-up observation.
Bendriss
A
A
Department of Clinical Pharmacology, Besançon University Hospital, France.
Bechtel
Y
Y
Paintaud
G
G
Bendriss
E K
EK
Joanne
C
C
Bresson-Hadni
S
S
Magnette
J
J
Becker
M C
MC
Gillet
M
M
Mantion
G
G
D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System; D003647:Debrisoquin / Q000378:metabolism*; D003915:Dextromethorphan / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases; D010641:Phenotype; D013997:Time Factors
D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin