Comparison of adverse drug reaction profiles of two tacrolimus formulations in rats

Immunopharmacol Immunotoxicol. 2012 Jun;34(3):434-42. doi: 10.3109/08923973.2011.618135. Epub 2011 Oct 4.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Drugs, Generic / adverse effects*
  • Drugs, Generic / pharmacology
  • Fibrosis
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Male
  • Pancreatic Diseases / chemically induced
  • Pancreatic Diseases / metabolism
  • Pancreatic Diseases / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Tacrolimus / adverse effects*
  • Tacrolimus / pharmacology

Substances

  • Drugs, Generic
  • Tacrolimus