[Interactions between theophylline and drug metabolizing liver enzymes in the rat].
Theophylline induces increase of hepatic cytochrome P-450 contents and P-450 dependent polysubstrate monooxygenases (e.g. p-nitroanisol-demethylase, 7-ethoxycoumarin-deethylase) in rats and other animals and in man. The purpose of this study is to investigate the long-term effect of theophylline on hepatic cytochrome P-450 and P-450 dependent enzyme activities in rats. P-450 content is enhanced after 6 days treatment with theophylline (150 mg/kg/d orally), but reaches the initial level after 28 days treatment. However, the P-450 dependent enzyme activities (7-ethoxycoumarin-deethylase, p-nitroanisol-demethylase) remain elevated. The in vitro inhibition of 7-ethoxycoumarin-deethylase by alpha-naphthoflavone and metyrapone suggests a mixed type induction by theophylline. Treatment of the animals with phenobarbital and theophylline or with benzo(alpha)pyrene and theophylline does not lead to an enhancement of P-450 content compared with a treatment solely by phenobarbital or benzo(alpha)pyrene. However, the simultaneous application of theophylline and phenobarbital increases the 7-ethoxycoumarin-deethylase and p-nitroanisol-demethylase activities compared with an exclusive phenobarbital treatment, whereas the benzo(alpha)pyrene effect is not enhanced by theophylline.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism; D005260:Female; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology*; D013997:Time Factors
D001580:Benzopyrenes; D013806:Theophylline; D006899:Mixed Function Oxygenases; D010634:Phenobarbital
Wechselwirkungen zwischen Theophyllin und den arzneimittelmetabolisierenden Leberenzymen der Ratte.