Pharmacokinetic and pharmacodynamic interaction study of diazepam and metoprolol.

Abstract

In 6 normotensive, healthy male volunteers the pharmacodynamic responses (blood pressure, heart rate; sedation index, tracking test, reaction time) to metoprolol (100 mg bid orally), diazepam (0.1 mg/kg intravenously) and to their combination were studied. The pharmacokinetics of diazepam were also compared in a cross-over experiment, with and without pretreatment by the beta-adrenoceptor antagonist to evaluate the possibility of a drug interaction. The pharmacodynamic and pharmacokinetic investigations indicated that metoprolol only slightly impaired the elimination of diazepam (18% decrease in total clearance, 25% increase in elimination half-life). The pharmacodynamics of metoprolol (17% decrease in heart rate, 17% decrease in diastolic RR) was not significantly altered by the bolus injection of diazepam. The extent of prolongation in choice reaction time (RT2) induced by diazepam was significantly (p = 0.001) more pronounced following the co-administration of metoprolol. However, the results of RT1, the tracking test and the sedation index did not indicate any increased effect due to the beta-blocking agent. It is concluded that concomitant treatment with metoprolol and diazepam causes only minor and clinically irrelevant changes in drug metabolism and drug response.