title: Altered metabolism of tacrolimus in hepatic veno-occlusive disease.
abstract: Tacrolimus is widely used for the prophylaxis and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT) and graft rejection in solid organ transplantation. The metabolism of tacrolimus has been reported to be impaired in association with liver dysfunction, mostly as documented in liver transplant recipients. Hepatic veno-occlusive disease (VOD) is one of the serious complications after allogeneic HSCT. It is characterized by jaundice, fluid retention, and painful hepatomegaly, caused by endothelial cell injury resulting from the toxicity of the conditioning regimen. The impaired metabolism of tacrolimus in hepatic VOD has not previously been reported in the literature. Here, we report the notable alteration in the metabolism of tacrolimus in two patients with hepatic VOD, in whom the half-lives of tacrolimus were markedly prolonged (288 and 146 h).
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. tmori@sc.itc.keio.ac.jp
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Rie
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakazato
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Shincihiro
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus