title: Population pharmacokinetics of cyclosporine in Korean adults undergoing living-donor kidney transplantation.
abstract: OBJECTIVE
  To estimate the population pharmacokinetic parameters of cyclosporine in Korean adults undergoing living-donor kidney transplantation, and to identify clinical factors affecting cyclosporine pharmacokinetics.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Single, 1600-bed, tertiary care academic medical center in Seoul, South Korea.
  
  
  METHODS
  Seventy-four living-donor kidney transplant recipients (mean age 42 yrs) receiving oral cyclosporine microemulsion as an immunosuppressant between January 1, 2001, and August 31, 2006.
  
  
  RESULTS
  Using nonlinear mixed-effects modeling (NONMEM) with first-order absorption and elimination, a total of 2394 whole-blood cyclosporine concentrations from the 74 patients were analyzed. The effects of several clinical covariates on cyclosporine pharmacokinetic parameters were evaluated over 12 months after transplantation. The absorption rate constant was fixed at 1.28 hour(-1), and the following population pharmacokinetic estimates were calculated: cyclosporine clearance 43.6 L/hour, apparent volume of distribution 1990 L, and interpatient variability for clearance (coefficient of variation) 17.69%. The clinical factors (covariates) that significantly affected cyclosporine pharmacokinetics were postoperative days, prednisolone dose (in mg/day), total bilirubin level (mg/dl), current body weight (in kg), and concurrent use of amlodipine.
  
  
  CONCLUSIONS
  This population pharmacokinetic model identified important sources of variability in cyclosporine pharmacokinetics. The model will help calculate cyclosporine dose requirements in renal transplant recipients according to specific clinical factors affecting cyclosporine clearance, and it will also be useful for therapeutic drug monitoring.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Ji
authors.forename: Mi-young
authors.initials: MY
authors.lastname: Kim
authors.forename: Hwi-yeol
authors.initials: HY
authors.lastname: Yun
authors.forename: Kyung Im
authors.initials: KI
authors.lastname: Kim
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
authors.forename: Kwang-il
authors.initials: KI
authors.lastname: Kwon
authors.forename: In-Wha
authors.initials: IW
authors.lastname: Kim
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Wan Gyoon
authors.initials: WG
authors.lastname: Shin
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Oh
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D044466:Asian People; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D056910:Republic of Korea; D012189:Retrospective Studies; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D004655:Emulsions; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone