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- W2073113067 abstract "Both verapamil and nifedipine are first-generation calcium-entry antagonist drugs which are eliminated by hepatic metabolism. To evaluate the effects of enzyme induction and suppression on the biotransformation of these compounds, liver homogenate fractions were prepared from male Fisher (F344) rats, which were either untreated, or injected intraperitoneally with phenobarbital or with SKF-525A prior to sacrifice. Known concentrations of verapamil or nifedipine were incubated with the 9,000 g supernatant, and the quantity of unchanged drug remaining after 10 min was measured. SKF-525A pretreatment significantly decreased the elimination (disappearance) rate of both calcium-entry antagonist compounds. Phenobarbital increased the rate of disappearance of verapamil, but had no effect on that of nifedipine. Difference spectra of hepatic microsomes to which verapamil had been added revealed a concentration-dependent, saturable interaction between drug and enzymes with spectral changes characteristic of type I' substrates for cytochrome P-450 monooxygenase(s). The spectral characteristic of microsomes to which nifedipine was added could not be determined because of drug absorption at 350-500 nm. These data imply that verapamil metabolism is mediated by the cytochrome P-450 monooxygenase(s), and that nifedipine metabolism likely involves hepatic enzyme systems other than those known to be induced by phenobarbital." @default.
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- W2073113067 date "1985-01-01" @default.
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- W2073113067 title "Effects of Phenobarbital and SKF-525A on in vitro Hepatic Metabolism of Verapamil and Nifedipine" @default.
- W2073113067 doi "https://doi.org/10.1159/000138060" @default.
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