| Autor: |
Zimmerman, Hyman J., Jacob, Leonard, Bassan, Harry, Gillespie, John, Lukacs, Larry, Abernathy, Charles O. |
| Zdroj: |
Experimental Biology and Medicine; September 1986, Vol. 182 Issue: 4 p511-514, 4p |
| Abstrakt: |
The adverse effects on an in vitromodel of oxmetidine, an H2-blocking agent which has been shown to produce hepatic injury in 1 to 4% of patients, were compared with those of cimetidine and ranitidine which have led to only rare instances of hepatic injury. Suspensions of hepatocytes, freshly isolated from Sprague-Dawley rats, were exposed to the three drugs. Oxmetidine, in concentrations of 3 × 10-3Mor greater, led to leakage of AST into the medium after 4 hr of incubation. Ranitidine and cimetidine, in concentrations up to 5 × 10-3M, produced no identifiable leakage. Pretreatment of rats with phenobarbital, 3-methylcholanthrene, or SKF 525A resulted in no significant enhancement or inhibition of the oxmetidine effects. These results suggest that the adverse effects of oxmetidine on the hepatocytes are produced by the native compound, not a metabolite. The positive correlation between in vivoand in vitrotoxicity supports the view that in vitrotesting may prove to be of use in predicting the hepatotoxic potential of a drug. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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