Propranolol does not alter flutoprazepam kinetics and metabolism in the rat.
The influence of propranolol on the disposition of flutoprazepam, a benzodiazepine derivative extensively biotransformed by hepatic microsomal oxidation, was evaluated in the rat. Propranolol was infused subcutaneously with osmotic minipumps (5 mg/day) to obtain steady-state concentrations of about 200 ng/ml. Flutoprazepam (5 mg/kg) was given intraperitoneally on the third day of propranolol infusion. There was some variability in flutoprazepam disposition, consistent with the concept of an extensive first-pass metabolism of high-extraction drugs. Propranolol had no significant effects on the kinetics of flutoprazepam or norflutoprazepam, an active metabolite possibly accounting for a substantial part of the parent compound's pharmacological and clinical effects. It was concluded that there is no evidence of any pharmacokinetic interaction between this beta-adrenoceptor blocker and flutoprazepam in the rat.
Conti
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Laboratory of Drug Metabolism, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Sarati
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Caccia
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D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005479:Flurazepam / Q000031:analogs & derivatives / Q000097:blood; D006207:Half-Life; D007260:Infusion Pumps; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C029163:flutoprazepam; D011433:Propranolol; D005479:Flurazepam; C020965:norflutoprazepam