title: Pharmacokinetics of CsA during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation.
abstract: We investigated the serial changes in the blood CsA concentration during the switch from continuous intravenous infusion to twice-daily oral administration in allogeneic hematopoietic stem cell transplant recipients (n=12). The microemulsion form of CsA, Neoral, was started at twice the last dose in intravenous infusion in two equally divided doses. The area under the concentration-time curve during oral administration (AUC(PO)) was significantly higher than the AUC during intravenous infusion (AUC(IV)) (median 7508 vs 6705 ng/ml x h, P=0.050). The median bioavailability of Neoral, defined as (AUC(PO)/DOSE(PO)) divided by (AUC(IV)/DOSE(IV)), was 0.685 (range, 0.45-1.04). Concomitant administration of oral voriconazole (n=4) significantly increased the bioavailability of Neoral (median 0.87 vs 0.54, P=0.017), probably due to the inhibition of gut CYP3A4 by voriconazole. Although the conversion from intravenous to oral administration of CsA at a ratio of 1:2 seemed to be appropriate in most patients, a lower conversion ratio may be better in patients taking oral voriconazole. To obtain a similar AUC, the target trough concentrations during twice-daily oral administration should be halved compared with the target concentration during continuous infusion.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Oshima
authors.forename: S
authors.initials: S
authors.lastname: Okuda
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Terasako
authors.forename: H
authors.initials: H
authors.lastname: Nakasone
authors.forename: S
authors.initials: S
authors.lastname: Kako
authors.forename: R
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Tanihara
authors.forename: T
authors.initials: T
authors.lastname: Higuchi
authors.forename: J
authors.initials: J
authors.lastname: Nishida
authors.forename: Y
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents; D019540:Area Under Curve; D001682:Biological Availability; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004357:Drug Synergism; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D016572:Cyclosporine; D065819:Voriconazole