Modification of drug metabolic processes by compounds which intervene with the function of cytochrome P-450 as a mono-oxygenase and as an oxidase.
Pregnenolone-16 alpha-carbonitrile, spironolactone, tocopherol acetate and ethanol were tested for their effect on lipid peroxidation using microsomal membranes or linoleic acid as substrates and Fe++/ascorbate or Fe++ as electron sources. The steroids had no effect on lipid peroxidation, tocopherol and ethanol presented potent and mild antioxidant activity, respectively. Pregnenolone-16 alpha-carbonitrile, spironolactone, ethanol and tocopherol acetate were examined for the effects on the body's response to drugs. It was found that the former three agents increased the resistance to zoxazolamine, hexobarbital and chlorzoxazone and tocopherol acetate increased only that against chlorzoxazone. The test compounds were examined for their effect on the in vivo reduction of p-nitrobenzoate and the in vitro metabolism of zoxazolamine, hexobarbital, ethylmorphine and procaine. The two steroids and ethanol enhanced the metabolism almost in all cases, while tocopherol acetate increased only ethylmorphine N-demethylation very significantly.
Tani
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E
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Thessaloniki, Greece.
Rekka
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E
Iconomidis
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Kourounakis
P N
PN
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008041:Linoleic Acids / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009579:Nitrobenzoates / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D008041:Linoleic Acids; D009579:Nitrobenzoates; D004364:Pharmaceutical Preparations; D014810:Vitamin E; D011285:Pregnenolone Carbonitrile; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases