Toprol XL - Clinical Pharmacology

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Although beta-adrenergic receptor blockade is useful in the treatment of angina, hyper-tension, and heart failure there are situations in which sympathetic stimulation is vital. In patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. In the presence of AV block, beta-blockade may prevent the neces-sary facilitating effect of sympathetic activity on conduction. Beta 2 -adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients.

In other studies, treatment with TOPROL-XL produced an improvement in left ventric-ular ejection fraction. TOPROL-XL was also shown to delay the increase in left ventricular end-systolic and end-diastolic volumes after 6 months of treatment.

Hypertension

The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competi-tive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity.

Clinical Trials

In controlled clinical studies, an immediate release dosage form of metoprolol has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics at dosages of 100Ð 450 mg daily. TOPROL-XL, in dosages of 100 to 400 mg once daily, has been shown to possess comparable ß 1 -blockade as conventional metoprolol tablets administered two to four times daily. In addition, TOPROL-XL administered at a dose of 50 mg once daily has been shown to lower blood pressure 24-hours post-dosing in placebo-controlled studies.

In controlled, comparative, clinical studies, immediate release metoprolol appeared comparable as an antihypertensive agent to propranolol, methyldopa, and thiazide-type diuretics, and affected both supine and standing blood pressure. Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihy-pertensive activity to drug plasma concentration, selection of proper dosage requires individual titration.