title: Pharmacokinetics of cyclosporine a conversion from twice-daily infusion to oral administration in allogeneic hematopoietic stem cell transplantation.
abstract: Twice-daily administration of cyclosporine A (CyA) has often been used for prophylaxis of acute graft versus host disease in allogeneic hematopoietic stem cell transplantation (allo-HSCT). But there have not been any reports that calculated the conversion ratio of the switch from twice-daily intravenous infusion to oral administration of CyA in adult patients. To establish the conversion ratio and the best strategy of twice-daily administration of CyA, the authors investigated the serial changes in the blood CyA concentration during the switch from twice-daily intravenous infusion to oral administration while maintaining high-peak concentration (over 1000 ng/mL) and calculated the bioavailability of Neoral, a micro emulsion cyclosporine, in 11 patients. All the patients underwent allo-HSCT with graft versus host disease prophylaxis consisting of CyA at a high-peak concentration of twice-daily infusion with short-term methotrexate and oral administration. Neoral was started at an oral dose, 2 times daily, at twice the latest dose of intravenous dose according to the bioavailability of healthy volunteers. Micafungin, a mild inhibitor of CYP3A4, was administered for prophylaxis against fungal infection. The total area under the concentration-time curve during oral administration (AUCpo) was nearly the same as AUC during intravenous infusion (AUCiv) (mean ± SD, 7206 ± 1557 ng·h·mL and 7783 ± 897.7 ng·h·mL, respectively). The bioavailability of Neoral, defined as F = AUCpo × DOSEiv/AUCiv × DOSEpo was 0.58 ± 0.15 (mean ± SD, range: 0.41-0.94). When patients were switched from twice-daily infusion to oral administration, the dose conversion ratio of 1:2 seemed to be appropriate. At that time, the target trough level of Neoral was nearly the same as that of the infusion.
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Inoue
authors.forename: Tasuku
authors.initials: T
authors.lastname: Saito
authors.forename: Kohei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishio
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kosugi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kato
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sakai
authors.forename: Masatomo
authors.initials: M
authors.lastname: Takahashi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Miura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine