title: Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in Chinese renal transplant recipients.
abstract: The aims of this study were to investigate the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Chinese renal transplant recipients, so as to help rational administration in clinical practice. We calculated pharmacokinetic parameters of tacrolimus from blood concentrations in steady state at day 28. Polymerase chain reaction restriction fragment length polymorphisms were used for CYP3A5 and MDR1 analysis. The results showed that the dose-adjusted area under the concentration time curve (AUC(0-12)) and renal clearance showed a significant difference between CYP3A5*1 carriers and the CYP3A5*3/*3 genotype (P < .01). In the following study, a distinction was made between carriers of CYP3A5*1/ vs CYP3A5*3/*3 seeking to investigate the influence of the MDR13435T>C polymorphism on tacrolimus pharmacokinetics. MDR1 3435T>C polymorphism did not affect any tacrolimus pharmacokinetic parameter in either group. Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC(0-12) of tacrolimus. In contrast, MDR1 3435T>C polymorphism was not an important factor in tacrolimus pharmacokinetics. Pharmacogenetic methods may be used prospectively to aid dose selection and individualize immunosuppressive therapy.
authors.affiliation: Organ Transplantation Institute of The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: G
authors.initials: G
authors.lastname: Rong
authors.forename: L
authors.initials: L
authors.lastname: Jing
authors.forename: L
authors.initials: L
authors.lastname: Deng-Qing
authors.forename: Z
authors.initials: Z
authors.lastname: Hong-Shan
authors.forename: Z
authors.initials: Z
authors.lastname: Shai-Hong
authors.forename: N
authors.initials: N
authors.lastname: Xin-Min
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D044466:Asian People / Q000235:genetics*; D016009:Chi-Square Distribution; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000208:ethnology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013256:Steroids / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D013256:Steroids; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D009173:Mycophenolic Acid; D016559:Tacrolimus