TY  - JOUR
PY  - 1984//
TI  - Diazepam/beta-adrenoceptor antagonist interactions
JO  - British journal of clinical pharmacology
A1  - Hawksworth, G.
A1  - Betts, T.
A1  - Crowe, A.
A1  - Knight, R.
A1  - Nyemitei-Addo, I.
A1  - Parry, K.
A1  - Petrie, J. C.
A1  - Raffle, A.
A1  - Parsons, A.
SP  - 69S
EP  - 76S
VL  - 17
IS  - Suppl 1
N2  - 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.<p /> <p>Language: en</p>
LA  - en
SN  - 0306-5251
UR  - http://dx.doi.org/
ID  - ref1
ER  -