Document Detail


Pharmacokinetics of Cyclosporine a Conversion from Twice-Daily Infusion to Oral Administration in Allogeneic Hematopoietic Stem Cell Transplantation.
MedLine Citation:
PMID:  23011175     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Yasuyuki Inoue; Tasuku Saito; Kohei Ogawa; Yuji Nishio; Shigeki Kosugi; Yoshinori Suzuki; Masayuki Kato; Hirotaka Sakai; Masatomo Takahashi; Ikuo Miura
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-24
Journal Detail:
Title:  American journal of therapeutics     Volume:  -     ISSN:  1536-3686     ISO Abbreviation:  Am J Ther     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9441347     Medline TA:  Am J Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, Division of Hematology and Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.
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