title: Cytochrome P450 3A4FNx011B as pharmacogenomic predictor of tacrolimus pharmacokinetics and clinical outcome in the liver transplant recipients.
abstract: OBJECTIVE
  Tacrolimus is a macrolide immunosuppressant used for prevention of allograft rejection in organ transplantation and metabolized in the liver and intestine by cytochrome P450 3A4 (CYP3A4) enzyme. A single nucleotide polymorphism (SNP) in the CYP3A4 promoter region has been identified. It has been shown that the presence of CYP3A4FNx011B allele (variant GG) is associated with a reduced catalytic activity of CYP3A4 in vivo. The aim of this study was to determine the role of CYP3A4FNx011B on tacrolimus dosing and clinical outcome in liver transplant recipients.
  
  
  METHODS
  Forty-eight liver transplant recipients were stratified according to the genotype. There were 32 wild-type (AA) patients and 5 homozygous variant (GG) and 11 (AG) heterozygous. Tacrolimus doses and trough concentrations as well as phenotypic data were collected in the first 10 days of the transplant.
  
  
  RESULTS
  The tacrolimus concentration was significantly higher in the wild (AA) group as compared to homozygous variant (GG) and heterozygous (AG) patients. Homozygous variant (GG) group had significantly lower dose requirements. However, no significant difference was observed in the concentration/dose ratio between all groups.
  
  
  CONCLUSIONS
  Based on our results, it may be concluded that CYP3A4FNx011B of recipient is an important factor influencing pharmacokinetic of tacrolimus, as patients with CYP3A4FNx011B polymorphism may require lower tacrolimus doses to maintain therapeutic levels. The dose reduction may not affect clinical outcomes after liver transplant.
authors.affiliation: College of Pharmacy, King Saud Bin Abdulaziz University for Health and Science, P.O. Box 22490, Riyadh 11426, Kingdom of Saudi Arabia.
authors.forename: Abdulkareem
authors.initials: A
authors.lastname: Albekairy
authors.forename: Abdulmalik
authors.initials: A
authors.lastname: Alkatheri
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Alan
authors.initials: A
authors.lastname: Hemming
authors.forename: Richard
authors.initials: R
authors.lastname: Howard
authors.forename: Alan
authors.initials: A
authors.lastname: Reed
authors.forename: Janet
authors.initials: J
authors.lastname: Karlix
mesh_terms: D000328:Adult; D000368:Aged; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D016559:Tacrolimus