title: Clinical and genetic factors affecting tacrolimus trough levels and drug-related outcomes in Korean kidney transplant recipients.
abstract: OBJECTIVE
  The purpose of this study was to characterize the effects of clinical and genetic variables on the pharmacokinetics and complications of tacrolimus during the first year after kidney transplantation.
  
  
  METHODS
  One hundred and thirty-two Korean kidney recipients who received tacrolimus were genotyped for ABCB1 (exons 12, 21, and 26) and CYP3A5 (intron 3). Tacrolimus trough levels, dose, or dose-adjusted trough levels and complications were compared among patients during the early stage (3, 7, 14, 30, and 90 days) and up to 1 year according to the genotypes.
  
  
  RESULTS
  A donor source-adjusted linear mixed model with multilevel analysis adjusting for age, body weight, hematocrit, and serum creatinine showed that CYP3A5 genotype is associated with dose-adjusted level of tacrolimus (p < 0.001). The influence of ABCB1 polymorphisms on the pharmacokinetics or complications of tacrolimus was less certain in our study. The incidence of acute rejections was significantly higher in recipients of cadaveric donor kidney (p < 0.05).
  
  
  CONCLUSIONS
  A generalized estimating equation model analysis showed that alopecia and hyperlipidemia were associated with dose-adjusted level of tacrolimus (p < 0.001). Genotype of CYP3A5 variants along with significant clinical covariates may be useful in individualizing tacrolimus therapy in kidney transplantation patients.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
authors.forename: In-Wha
authors.initials: IW
authors.lastname: Kim
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Moon
authors.forename: Eunhee
authors.initials: E
authors.lastname: Ji
authors.forename: Kyung Im
authors.initials: KI
authors.lastname: Kim
authors.forename: Nayoung
authors.initials: N
authors.lastname: Han
authors.forename: Sung Ju
authors.initials: SJ
authors.lastname: Kim
authors.forename: Wan Gyoon
authors.initials: WG
authors.lastname: Shin
authors.forename: Jongwon
authors.initials: J
authors.lastname: Ha
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Oh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D065095:Calcineurin Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D016903:Drug Monitoring; D005260:Female; D056726:Genetic Association Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; 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; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus