ISSN:
1573-8744
Keywords:
metoprolol
;
α-OH-metoprolol
;
active metabolites
;
pharmacokinetics
;
β- blocking effect
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The plasma levels and the β- blocking effect of metoprolol and its active metabolite α- hydroxymetoprolol have been studied after i.v. bolus injections of the substances to dogs. For both substances the β- blockade increased with the dose, and there was a linear relationship between percent reduction in exercise heart rate and the logarithm of plasma concentration. The dose of the metabolite, however, had to be 5 times higher than that of metoprolol to induce the same degree of β- blockade. Because of differences in the volume of distribution, 2.0 liters/kg for α- OH-metoprolol and 3.5 liters/kg for metoprolol, the 5 times higher dose of α- OH-metoprolol resulted in 10 times higher plasma levels of the metabolite than of metoprolol. α- OH-Metoprolol was more slowly eliminated (t1/2∼7.0 hr, total body clearance ∼3.5 ml-kg−1-min−1) than metoprolol (t1/2∼2.0 hr, total body clearance ∼20.0 ml-kg−1-min−1). Approximately 5% of an i.v. dose of metoprolol was metabolized to α- OH-metoprolol. The half-life of the endogenously formed metabolite was the same as after an i.v. dose of the compound.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01062389
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