title: Population pharmacokinetics and pharmacodynamics of busulfan with GSTA1 polymorphisms in patients undergoing allogeneic hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  A population pharmacokinetic (PPK) analysis was conducted to describe the influence of GSTA1 polymorphisms on intravenous busulfan in adults undergoing allogeneic hematopoietic stem cell transplantation.
  
  
  METHODS
  A PPK model was developed from 36 patients by a one-compartment model with first-order elimination.
  
  
  RESULTS
  The typical value of clearance and volume of distribution were 11.0 l/h and 42.4 l, respectively. Clearance decreased by 15% and area under the concentration-time curves (AUCs) increased with GSTA1 variants compared with wild-type (both p < 0.05). Subtherapeutic AUCs were seen only in wild-type patients.
  
  
  CONCLUSIONS
  To our knowledge, this is the first PPK study to suggest that GSTA1 polymorphisms in adults are associated with busulfan PK.
authors.affiliation: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Boyoon
authors.initials: B
authors.lastname: Choi
authors.affiliation: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Myeong Gyu
authors.initials: MG
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Han
authors.affiliation: College of Pharmacy, Chonnam National University, Gwangju, Korea.
authors.forename: Therasa
authors.initials: T
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Gachon University, Incheon, Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Ji
authors.affiliation: Department of Internal Medicine, Seoul National University Medicine of College, Seoul, Korea.
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: In-Wha
authors.initials: IW
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Oh
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D002066:Busulfan / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011110:Polymorphism, Genetic / Q000235:genetics; D011153:Population; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C484555:GSTA1 protein, human; D005982:Glutathione Transferase; D002066:Busulfan
keywords: GSTA1; alloHSCT; allogeneic hematopoietic stem cell transplantation; busulfan; clinical outcomes; genetic polymorphisms; glutathione s-transferase a1; population pharmacokinetics