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

Research output: Contribution to journalArticle

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

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Famotidine
Histamine H2 Receptors
Ranitidine
Cimetidine
Drug Interactions
Cyclosporine
Sprague Dawley Rats
Serum
Creatinine
Liver
Fatty Liver
Drug-Related Side Effects and Adverse Reactions
Cytochrome P-450 Enzyme System
Ulcer
Control Groups
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

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

Cite this

Evidence of drug interaction between cyclosporin A and H2-receptor antagonists (cimetidine, ranitidine and famotidine) in Sprague-Dawley rats. / Filingeri, V.; Giacomelli, R.; Famularo, G.; Rosati, R.; Nardi, S.; Calogero, A.; Iacona, A.; Stortoni, F.; Cramarossa, L.; Sacchetti, S.; Cervelli, V.; Tonietti, G.; Casciani, C. U.

In: Drugs under Experimental and Clinical Research, Vol. 15, No. 4, 1989, p. 159-164.

Research output: Contribution to journalArticle

Filingeri, V, Giacomelli, R, Famularo, G, Rosati, R, Nardi, S, Calogero, A, Iacona, A, Stortoni, F, Cramarossa, L, Sacchetti, S, Cervelli, V, Tonietti, G & Casciani, CU 1989, 'Evidence of drug interaction between cyclosporin A and H2-receptor antagonists (cimetidine, ranitidine and famotidine) in Sprague-Dawley rats', Drugs under Experimental and Clinical Research, vol. 15, no. 4, pp. 159-164.
Filingeri, V. ; Giacomelli, R. ; Famularo, G. ; Rosati, R. ; Nardi, S. ; Calogero, A. ; Iacona, A. ; Stortoni, F. ; Cramarossa, L. ; Sacchetti, S. ; Cervelli, V. ; Tonietti, G. ; Casciani, C. U. / Evidence of drug interaction between cyclosporin A and H2-receptor antagonists (cimetidine, ranitidine and famotidine) in Sprague-Dawley rats. In: Drugs under Experimental and Clinical Research. 1989 ; Vol. 15, No. 4. pp. 159-164.
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T1 - Evidence of drug interaction between cyclosporin A and H2-receptor antagonists (cimetidine, ranitidine and famotidine) in Sprague-Dawley rats

AU - Filingeri, V.

AU - Giacomelli, R.

AU - Famularo, G.

AU - Rosati, R.

AU - Nardi, S.

AU - Calogero, A.

AU - Iacona, A.

AU - Stortoni, F.

AU - Cramarossa, L.

AU - Sacchetti, S.

AU - Cervelli, V.

AU - Tonietti, G.

AU - Casciani, C. U.

PY - 1989

Y1 - 1989

N2 - 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.

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