Tacrolimus and nonsteroidal anti-inflammatory drugs: an association to be avoided

Am J Nephrol. Jul-Aug 2005;25(4):327-34. doi: 10.1159/000086569. Epub 2005 Jun 21.

Abstract

Background: Tacrolimus (FK) and nonsteroidal anti-inflammatory drugs (NSAIDs) can cause acute nephrotoxicity. The expanding use of tacrolimus and the intense consumption of NSAIDS increase the chances of their simultaneous use.

Methods: Rats receiving a nonselective COX inhibitor (diclofenac, D) and FK or a selective COX-2 inhibitor (rofecoxib, RO) and FK were treated with FK (2 mg/kg/day), D (10 mg/kg/day), RO (3 mg/kg/day), FK+D, FK+RO and vehicle for 7 days on low-salt diet.

Results: Both associations significantly impaired glomerular filtration rate (GFR; 0.63 +/- 0.06 ml/min/100 g in FK+D, 0.83 +/- 0.06 ml/min/100 g in FK+RO) which did not occur with single drug therapy (0.98 +/- 0.03 ml/min/100 g in D, 1.06 +/- 0.04 ml/min/100 g in RO, 0.99 +/- 0.05 ml/min/ 100 g in FK) or vehicle (1.10 +/- 0.05 ml/min/100 g). GFR decrease was significantly higher with FK+D. GFR impairment occurred without RBF or RVR major changes. Mild tubular vacuolization and dilatation and acute degenerative changes were observed in tubular cells. FK+D animals showed a marked weight loss, not observed in the other groups. FK+NSAIDs association decreased FK blood levels (1.73 +/- 0.3 ng/ml in FK+D, 1.8 +/- 0.3 ng/ml in FK+RO, 3.2 +/- 0.4 ng/ml in FK, p < 0.05).

Conclusions: The association of FK and nonselective or COX-2 selective NSAIDs in salt-depleted animals caused a significant GFR impairment and decreased FK blood levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / pharmacology
  • Diclofenac / adverse effects
  • Diclofenac / pharmacology
  • Drug Synergism
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / pharmacology
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Lactones / adverse effects
  • Lactones / pharmacology
  • Male
  • Models, Animal
  • Rats
  • Sulfones / adverse effects
  • Sulfones / pharmacology
  • Tacrolimus / adverse effects*
  • Tacrolimus / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Immunosuppressive Agents
  • Lactones
  • Sulfones
  • rofecoxib
  • Diclofenac
  • Tacrolimus