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.

Filingeri, V., Giacomelli, R., Famularo, G., Rosati, R., Nardi, S., Calogero, A., et al. (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, 15(4), 159-164.

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

FILINGERI, VINCENZINO;ROSATI, ROBERTO;CERVELLI, VALERIO;CASCIANI, CARLO UMBERTO
1989-01-01

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/18 - Chirurgia Generale
English
cimetidine; cyclosporin a; cytochrome p450; famotidine; ranitidine; alanine aminotransferase blood level; animal experiment; aspartate aminotransferase blood level; creatinine blood level; drug blood level; drug interaction; drug metabolism; fatty liver; histology; intraperitoneal drug administration; kidney function; liver toxicity; nonhuman; priority journal; rat; Alanine Transaminase; Animal; Aspartate Aminotransferases; Cimetidine; Creatinine; Cyclosporins; Drug Interactions; Famotidine; Histamine H2 Antagonists; Kidney; Liver; Male; Ranitidine; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Thiazoles
Filingeri, V., Giacomelli, R., Famularo, G., Rosati, R., Nardi, S., Calogero, A., et al. (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, 15(4), 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, Cu
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/50655
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