title: Efficacy of oral treatment with tacrolimus in the renal transplant model in cynomolgus monkeys.
abstract: Many studies have examined the efficacy of tacrolimus in rats and dogs, but few have reported its evaluation in cynomolgus monkeys. The aim of this study was to clarify the efficacy of tacrolimus in a cynomolgus monkey renal transplant model based on the efficacy of various doses. Monkeys that had undergone renal transplant were treated with a vehicle or 0.5, 1.0, or 2.0 mg/kg of tacrolimus by oral administration. Tacrolimus administration prolonged animal survival in a dose-dependent manner, and the median survival time (MST) was 11, 21, and >90 days for the 0.5, 1.0, and 2.0 mg/kg tacrolimus groups, respectively. The MST of the vehicle group was 6 days. Histopathological analyses of all transplanted kidneys were also performed. Typical pathological findings of acute rejection were observed in both the vehicle and tacrolimus (0.5 and 1.0 mg/kg)-treated groups. Only limited mononuclear cell infiltration and hemorrhage were present in the tacrolimus (2.0 mg/kg)-treated group. In conclusion, 2.0 mg/kg was considered to be a therapeutic dose in this model, and 0.5 or 1.0 mg/kg could be used for a study when efficacy of a new compound is evaluated in a combination therapy with tacrolimus.
authors.affiliation: Department of Immunology, Pharmacology Research Labs, Astellas Pharma, Inc., Japan. fumitaka.kinugasa@jp.astellas.com
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kinugasa
authors.forename: Itsuo
authors.initials: I
authors.lastname: Nagatomi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Masashi
authors.initials: M
authors.lastname: Maeda
authors.forename: Jun
authors.initials: J
authors.lastname: Hirose
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Fukahori
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ooshima
authors.forename: Takahisa
authors.initials: T
authors.lastname: Noto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Higashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Seki
authors.forename: Seitaro
authors.initials: S
authors.lastname: Mutoh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006470:Hemorrhage / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus