Diazepam/beta-adrenoceptor antagonist interactions.
The effects of diazepam on the pharmacokinetics and pharmacodynamics of two lipophilic beta-adrenoceptor antagonists (propranolol and metoprolol) and a hydrophilic beta-adrenoceptor antagonist (atenolol) were compared in 12 subjects. Administration of propranolol and metoprolol produced small increases in the AUC0-8h for diazepam compared with placebo (P less than 0.05 for metoprolol). Atenolol had no significant effect on the AUC0-8h for diazepam. The increase in the AUC0-8h was accompanied by increases in the plasma concentrations of N-desmethyldiazepam. Diazepam had no significant effect on the pharmacokinetics of either propranolol or atenolol. The pharmacokinetic interaction could be attributed to inhibition of diazepam metabolism by the lipophilic beta-adrenoceptor antagonists. The pharmacodynamic studies showed that when compared with placebo or atenolol there was a significant impairment of kinetic visual acuity (KVA) when diazepam was co-administered with metoprolol. Although there was a significant correlation (P less than 0.02) between plasma concentrations of diazepam and impairment of KVA, the pharmacodynamic interactions may not be due solely to the small pharmacokinetic interaction observed.
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D004644:Emotions / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D003708:Nordazepam / Q000097:blood; D011433:Propranolol / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D014792:Visual Acuity / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D003708:Nordazepam; D011433:Propranolol; D008790:Metoprolol; D003975:Diazepam