Plasma Propranolol Levels Research Articles

Effect of route of administration on the relationship between -adrenergic blockade and plasma propranolol level.

The antagonism of isoproterenol‐induced tachycardia by orally and intravenously administered propranolol was measured in 5 subjects and related to the plasma propranolol concentration. Two hours after oral administration of a single dose of propranolol, the degree of beta blockade associated with a given plasma propranolol concentration was greater than that seen with the same concentration achieved by intravenous administration. After 6 hours, this disparity was no longer apparent. During long‐term 6 hour administration, the effect of the twenty‐first dose both 2 and 6 hours after administration was the same as that resulting from similar plasma levels achieved by intravenous administration. These findings can be explained by the formation after single oral doses of an active metabolite, 4‐hydroxypropranolol, which has a shorter half‐life than does the parent drug. This metabolite is not produced during intravenous administration of single doses. However, at the end of a 6 hour dosage interval and after chronic oral administration, the effects of propranolol could be attributed entirely to circulating levels of the parent drug.

Plasma propranolol levels associated with suppression of ventricular ectopic beats.

The plasma propranolol levels associated with the abolition of chronic, stable ventricular ectopic beats have been studied. Racemic propranolol (DL) suppressed the ectopic foci at plasma levels of 40-85 ng/ml in eight patients, but levels of 70-200 ng/ml were unsuccessful in four patients. Dextro-(D) propranolol levels of 180-310 ng/ml were ineffective in four patients who had previously responded at levels of 60-75 ng/ml of racemic propranolol. The significance of the sympathetic nervous system in the genesis of ectopic beats is discussed. It is concluded that propranolol is clinically effective by virtue of its beta-adrenergic blocking activity.

Plasma Propranolol Levels in the Quantitative Assessment of -adrenergic Blockade in Man

Plasma propranolol levels associated with reductions in endogenous and exogenous cardiac beta-stimulation were determined in normal people. The levels associated with a given degree of blockade of exercise-induced tachycardia were about three times greater after intravenous administration than after oral administration. This shows that an active metabolite of propranolol is formed only after the drug is taken by mouth. The greatest reduction in the tachycardia of strenuous exercise was associated with plasma levels of 40 ng./ml. with oral administration and 100 ng./ml. with intravenously administered propranolol.The effect on isoprenaline-induced tachycardia following intravenously administered propranolol showed that the dose ratio for isoprenaline was about 30 with plasma levels of 100 ng./ml. and 10 with levels of 10-20 ng./ml. These plasma levels give 100% and 20-30% blockade of exercise-induced tachycardia. These findings suggest that some of the therapeutic effects of propranolol may be unrelated to beta-adrenergic blockade.

Plasma propranolol levels in adults With observations in four children

Plasma levels of the f3‐adrenergic‐blocking drug, propranolol, have been measured fluorometrically in man after oral and intravenous administration. Following oral administration, peak plasma levels in 5 sub/ects varied sevenfold, while, after intravenous administration, levels in the same sub/ects varied only twofold, indicating considerable variability among individuals in the amount of drug reaching the systemiC circulation after oral administration. However, plasma levels were relatively constant in sub/ects given repeated, single doses. The plasma half‐life of the drug was 2.3 hours after intravenous administration. A plasma half‐life of 3.2 hours was found after oral administration; its greater duration was attributed to continuing absorption. After intravenous administration, the rate of decline of the levels of propranolol in the plasma was biexponential, and the volume of distribution during the late phase of elimination was found to be about 150 liters, indicating concentration of the drug in the tissues. The drug was administered orally to 4 children at dose levels calculated on the basis of body weight and on the basis of body surface area. It was found that a dose intermediate to the two tested would be required to obtain plasma levels approximating the average level in adults given an equivalent dose.