title: Comparison of adverse drug reaction profiles of two tacrolimus formulations in rats.
abstract: Tacrobell(®) (TB) is a generic tacrolimus which showed the comparable efficacy to original product, Prograf(®) (PG) in renal transplantation, but toxicity between two drugs is unclear. The aim of this study was to compare the toxicity between these two formulations. TB and PG (0.5, 1 and 2 mg/kg/day) was administered to rats for 4 weeks. The rat survival rate, kidney, liver and pancreas injury was investigated. The survival rate was similar between TB- and PG-treated rats. TB and PG induced renal dysfunction in a dose-dependent manner. Compared to PG treatment in equal dose, TB treatment reduced urinary creatinine clearance in a less degree and renal interstitial fibrosis was comparable between two regimens. The r-glutamyl transpeptidase was aggravated by tacrolimus treatment, and this was not different between TB and PG treatment. In the intraperitoneal glucose tolerance test, a significant diabetogenic effect was observed in all tacrolimus treated-rats. The glucose tolerance of TB-treated rats was similar to those of PG-treated rats in each dose. The decrement in pancreatic β-cell mass by tacrolimus showed the dose-dependent response and it was comparable between TB and PG treatment. In conclusion, TB is similar to PG in terms of nephrotoxicity, hepatoxicity and diabetogenic effect.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: HyeonSeok
authors.initials: H
authors.lastname: Hwang
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Ghee
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Song
authors.forename: ShangGuo
authors.initials: S
authors.lastname: Piao
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D016568:Drugs, Generic / Q000009:adverse effects* / Q000494:pharmacology; D005355:Fibrosis; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D016568:Drugs, Generic; D016559:Tacrolimus