title: Population pharmacokinetic study of cyclosporine in the hematopoietic stem cell transplant recipients.
abstract: OBJECTIVE
  The aim of this study is to investigate the population pharmacokinetics (PopPK) of cyclosporine (CsA) in the Chinese hematopoietic stem cell transplantation (HSCT) recipients for promoting the individualization of CsA administration.
  
  
  METHODS
  A total of 887 retrospective drug monitoring data points were collected from 58 HSCT recipients. Whole blood samples were collected at predose (C0) and 2 hours (C2) post dose. The administration of CsA was intermittent intravenous infusion, continuous intravenous infusion and oral. Population modeling was performed using the NONMEM (nonlinear mixedeffect modeling) program. A one compartment pharmacokinetic model was used to fit the data.
  
  
  RESULTS
  Body surface area (BSA), administration route and postoperative days were identified as significant covariates for clearance (CL) according to the final model: CL = 31.0 × (BSA/1.59)0.761 × (ROUT) × (POD), where ROUT was 1.91 if the administration route was intravenous infusion, otherwise it is equal to 1. The POD was 0.818, 0.753, 0.539, and 0.509 for posttransplant Days 0 - 10, 11 - 20, 21 - 30 and more than 30 days, respectively. Administration route was a significant covariate for volume (V) according to the final model: V = 192 × (ROUT), where ROUT was 4.10, 3.63 and 1 when the administration route was continuous intravenous infusion, intermittent intravenous infusion and oral. The other covariates were not identified as a significant effect on CsA pharmacokinetic parameters.
  
  
  CONCLUSIONS
  Body surface area, administration route and postoperative days should be considered in individual pharmacotherapy of cyclosporine for HSCT patient to achieve the desired therapeutic target.
authors.affiliation: Department of Pharmacy, Base for Clinical Trial, Peking University First Hospital, Beijing 100034, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Sheng
authors.forename: Jun-yu
authors.initials: JY
authors.lastname: Xu
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Bi
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Yi-min
authors.initials: YM
authors.lastname: Cui
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D044466:Asian People; D001830:Body Surface Area; D002648:Child; D002675:Child, Preschool; D002681:China; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D018380:Hematopoietic Stem Cell Transplantation / Q000208:ethnology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine