Diazepam/beta‐adrenoceptor antagonist interactions.

Abstract

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. 1984 The British Pharmacological Society