Tacrolimus dosing in Chinese renal transplant patients is related to MDR1 gene C3435T polymorphisms.
Tacrolimus is an immunosuppressive drug with narrow therapeutic range and wide interindividual variations in its pharmacokinetics. P-glycoprotein (P-gp) plays an important role in the absorption metabolism of tacrolimus. The polymorphism C3435T of MDR1, the gene coding P-gp, may influence the expression and activity of P-gp. The aim of this study was to evaluate whether C3435T polymorphism was associated with the tacrolimus concentration/dose ratio. Sixty-six Chinese renal transplant patients enrolled in this study were surveyed for body weight and dosage and concentration of tacrolimus as well as MDR1 genotype by polymerase chain reaction followed by restriction fragment length polymorphism analysis. The results showed a significant association between tacrolimus levels per dose mg/kg/d and MDR1 gene C3435T polymorphism (P < .05). The CC patients displayed a lower tacrolimus level per dose than CT/TT patients. Pharmacogenetic methods might be employed prospectively to help dose selection and to individualize immunosuppressive therapy.
Li
D
D
Organ Transplantation, The Third Xiangya Hospital, Changsha, Hunan, China.
Gui
R
R
Li
Jin
J
Huang
Z
Z
Nie
Xinmin
X
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001835:Body Weight; D002681:China; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016559:Tacrolimus