Abstract
The effects of two Ca 2+ antagonists nifedipine (NF) and diltiazem (DL) and of the nonselective β-adrenergic blocking agent propranolol (PR) on the hexobarbital (HB) sleeping time and on the activity of some liver drug-metabolizyng enzyme systems in male Wistar rats were studied. Two h after single oral administaration PR (50 mg/kg) did not change HB sleeping time, while NF (50 mg/kg) and DL (30 mg/kg) prolonged it by 171.2 and 99.6%, respectively. Coadmistration of PR with DL or with NF significantly prolonged HB sleep by 240.7 and 129%, respectively. Only NF increased aniline 4-hidroxylase (AH) activity (by 92%) and the total P-450 content (by 24%). PR and NF increased cytochrome b5 content and this effect was also observed with the combinations PR+NF (by 109%) and PR+DL (by 102%). The NADPH cytochrome P-450 reductase activity was significantly decreased by NF and DL and after their combination with PR. The ethymorphine- N-demethylase (EMND) and amidopyrine- N-demethylase (APND) activities were not changed. The effects of PR, NF and DL administrated alone or in combination on liver oxidative metabolism are considered as possible mechanisms of drug interactions.
Published Version
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