Evidence of drug interaction between cyclosporin A and H2-receptor antagonists (cimetidine, ranitidine and famotidine) in Sprague-Dawley rats

V. Filingeri, R. Giacomelli, G. Famularo, R. Rosati, S. Nardi, A. Calogero, A. Iacona, F. Stortoni, L. Cramarossa, S. Sacchetti, V. Cervelli, G. Tonietti, C. U. Casciani

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Abstract

H2-receptor antagonists, such as cimetidine (C), ranitidine (R) and famotidine (F) seem to be effective in the prevention and treatment of stress ulcer in transplant recipients receiving cyclosporin A (CyA). The aim of this study was to detect the possible synergistic nephro- and hepato-toxicity of these drugs, assaying the serum creatinine (SC), ALT, AST levels, and the histological features of 45 young male Sprague-Dawley rats, divided into nine groups of five rats each. After 10 days of treatment the results showed: (i) serum CyA levels were increased in the group receiving daily CyA (5 mg/kg) + R(5 mg/kg) (2430 ± 403 ng/ml; p <0.05 vs. controls) and the group receiving daily CyA (5 mg/kg) ± C(10 mg/kg) (2440 ± 265 ng/ml; p <0.01 vs. controls); (ii) ALT and AST levels were increased in this latter group (ALT 223 ± 133 UL, AST 114.67 ± 39 UL; p <0.01 vs. controls); (iii) SC levels were normal; and (iv) steatosis of the liver was observed in these two groups. These findings suggest that C and R, but not F, may inhibit the hepatic cytochrome P-450 which are involved in the oxidative metabolism of the drugs. Furthermore, the high serum CyA levels seem to play a major role in the appearance of biochemical and histological damage to the liver.

Original languageEnglish
Pages (from-to)159-164
Number of pages6
JournalDrugs under Experimental and Clinical Research
Volume15
Issue number4
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology (medical)
  • Drug Discovery
  • Pharmacology

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