title: Pharmacogenetics of tacrolimus: ready for clinical translation?
abstract: Tacrolimus (Tac) exhibits an interindividual pharmacokinetic variability that affects the dose required to reach the target concentration in blood. Tac is metabolized by two enzymes of the cytochrome P450 family, CYP3A5 and CYP3A4. The effect of theCYP3A5 genotype on Tac bioavailability has been demonstrated, and the main determinant of this pharmacogenetic effect is a single-nucleotide polymorphism (SNP) in intron 3 ofCYP3A5(6986 A>G; SNP rs776746; also known asCYP3A5*3). The mean dose-adjusted blood Tac concentration was significantly higher amongCYP3A5*3homozygotes than that of carriers of the wild-type allele (CYP3A5*1). In a recent prospective study, a group of kidney transplant patients received a Tac dose either according to theCYP3A5genotype (the adapted group) or according to the standard regimen (the control group). All patients received induction therapy with mycophenolate mofetil, corticosteroids, and either basiliximab or intravenous anti-thymocyte globulin. Patients in the adapted-dose group required 3-8 days (median 6 days) to reach the target range compared with 3-25 days (median 7 days) in the control group (P=0.001). The total number of dose modifications was also lower in the adapted-dose group. This study also suggested that theCYP3A5genotype might contribute minimally to the reduction of early acute rejection. However, additional studies are necessary to determine whether the pharmacogenetic approach could help reduce the necessity for induction therapy and co-immunosuppressors.
authors.affiliation: Genética Molecular, Hospital Universitario Central de Asturias , Oviedo, Spain ; Departamento de Medicina, Universidad de Oviedo , Oviedo, Spain ; Fundación Renal 'Iñigo Alvarez de Toledo' , Madrid, Spain ; Red de Investigación Renal , Redinren, Spain.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.affiliation: Genética Molecular, Hospital Universitario Central de Asturias , Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tavira
authors.affiliation: Red de Investigación Renal , Redinren, Spain ; Inmunología, Hospital Universitario Central de Asturias , Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Suárez-Álvarez
authors.affiliation: Fundación Renal 'Iñigo Alvarez de Toledo' , Madrid, Spain ; Red de Investigación Renal , Redinren, Spain ; Inmunología, Hospital Universitario Central de Asturias , Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.affiliation: Departamento de Medicina, Universidad de Oviedo , Oviedo, Spain ; Red de Investigación Renal , Redinren, Spain ; Nefrología, Hospital Universitario Central de Asturias , Oviedo, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Díaz-Corte
authors.affiliation: Departamento de Medicina, Universidad de Oviedo , Oviedo, Spain ; Fundación Renal 'Iñigo Alvarez de Toledo' , Madrid, Spain ; Red de Investigación Renal , Redinren, Spain ; Nefrología, Hospital Universitario Central de Asturias , Oviedo, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.affiliation: Genética Molecular, Hospital Universitario Central de Asturias , Oviedo, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
keywords: cytochromes P450; pharmacogenetics; pharmacokinetics; renal transplantation; tacrolimus