title: Metabolism for cyclosporin A during liver regeneration after partial hepatectomy in rats.
abstract: OBJECTIVE
  To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immunosuppressive drug used in transplantation in a partially hepatectomized rat model.
  
  
  METHODS
  CyA was administered to rats that underwent a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; (group 1) water, (group 2) 5 mg/kg CyA, (group 3) 10 mg/kg CyA. On postoperative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver regeneration ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-polymerase chain reaction method to determine albumin and cytochrome p450 expression.
  
  
  RESULTS
  The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity.
  
  
  CONCLUSIONS
  These data indicate that the p-450 activity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepatectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.
authors.affiliation: Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nagayoshi
authors.forename: Yujo
authors.initials: Y
authors.lastname: Kawashita
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kamohara
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Takatsuki
authors.forename: Shungo
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Soyama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tokai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hidaka
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Tajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D004305:Dose-Response Relationship, Drug; D006498:Hepatectomy; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery*; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D012333:RNA, Messenger; D012709:Serum Albumin; D016572:Cyclosporine; D001189:Aryl Hydrocarbon Hydroxylases; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A