title: Pharmacokinetics of cyclosporine A at a high-peak concentration of twice-daily infusion and oral administration in allogeneic haematopoietic stem cell transplantation.
abstract: OBJECTIVE
  The most appropriate immunosuppressive strategy with calcineurin inhibitors for the prevention of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) has not yet been established. To estimate the safety and efficacy of a new strategy, we investigated the pharmacokinetics of cyclosporine A (CyA) delivered by twice-daily infusion and oral administration maintained with a peak level above 1000 ng/mL to keep 24 h area under the concentration-time curve (AUC0-24) higher than 10 000 ng·h/mL in 12 patients.
  
  
  METHODS
  Cyclosporine A was started as a twice-daily infusion at 1·5 mg/kg and then orally administered at twice the infusion dose to maintain the trough blood concentration between 200 and 500 ng/mL, and with a peak level above 1000 ng/mL. Serial blood samples were collected at 0, 1, 2, 3, 5, 8 and 12 h after CyA dosing (C0, C1, C2, C3, C5, C8 and C12) on days 14-21 after transplantation and on days 7-14 after switching to oral administration, and the AUC was calculated.
  
  
  RESULTS
  In all patients, the AUC0-24 for both twice-daily infusion and oral administration was higher than 10 000 ng·h/mL. Two close relationships were observed between AUC0-12 and the C3 for infusion and between AUC0-12 and the C8 for oral administration. None of the patients had grades 3-4 aGVHD or other serious complications.
  
  
  CONCLUSIONS
  This strategy was well tolerated, and the C3 for twice-daily infusion and the C8 for oral administration were the optimal points for monitoring of CyA concentration in the early phase of transplantation.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, St. Marianna University, School of Medicine, Kawasaki, Japan. inoyasu@med.nihon-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nishio
authors.forename: S
authors.initials: S
authors.lastname: Kosugi
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Shibuya
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: I
authors.initials: I
authors.lastname: Miura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine