The H2-receptor antagonist, cimetidine, through binding of its imidazole ring to cytochrome P-450, has been known to inhibit drug metabolism, and the antituberculous drug, rifampicin, through microsomal enzyme induction, has been known to
increase
drug
metabolism.
The intermediate metabolites of halothane appear to be involved in the etiology of halothaneinduced hepatotoxicity. This study was done to determine the effect of cimetidine on halothane hepatotoxicity in rats pretreated with rifampicin.
Ninty six Sprague-Dawley rats were divided into three groups. Saline was administered orally daily for 7 days in group I (N=31). Rifampicin (100mg/kg) was administered orally daily for 7 days in group II(N=33) and group III(N=32). Cimetidine
(180mg/kg)
was injected intraperitoneally one hour before halothane anesthesia in group III All of the three groups were exposed to halothane-N2O-O2(1%-3L/min-3L/min) for two hours 24 hours after the last treatment with saline or rifampicin.
Blood sampling was doen before any treatment as control. Blood sampling and hepatectomy for light microscopic examination 24 hours after halothane anesthesia were done in one half of the rats from each group and the remaining were examined 96
hours
after halothane anesthesia. The measurements we examined were values of liver function test(alanine aminotransferase: ALT) and aspartate aminotranferase: AST), metabolites of halothane (bromide and fluoride) and the histologic scores of light
microscopin findings of liver tissue 24 hours or 96 hours after halothane anesthesia.
@ES The results were as follows;
@EN 1. The values of liver function test 24 hours after halothane anesthesia showed increasing tendency in all three groups, but there were no statistical significance in all three group except the value of AST in group III.
2. The values of ALT and AST 96 hours after halothane anestheisa decrease and showed significant statistical difference from those fo 24 hours after anesthesia in group II.
3. Serum concentrations of bromide and fluoride 24 hours or 96 hours after halothane anesthesia showed no significant statistical differences among three groups. But bromide conentration 96 hours after halothane anesthesia was less than the
values
24
hours after halothane anesthesia (p<0.05).
4. The histologic evidences of hipatic changes were not shown in all group 24 hours and 96 hours after anesthesia.
The above results concluded that neither cimetidine nor rifampicin does affect halothane metabolism and hepatic changes after halothane anesthesia.
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