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Arzneimittel-Forschung

Variation of pharmacokinetics after oral administration of slow-release metoprolol tablets and pharmacogenetic considerations.


PMID 1418033

Abstract

The maximum plasma concentrations (Cmax) after oral administration of 120 mg tablets of slow-release metoprolol (CAS 37350-58-6) to 75 Japanese healthy male volunteers and 15 arrhythmic patients were measured. Extensive and poor metabolizers after oral administrations of slow-release metoprolol tablets were classified by means of the frequency distribution of Cmax values. In addition, the frequency distribution of Cmax values after oral administration of slow-release metoprolol 120 mg tablets was compared with that of conventional metoprolol 40 mg tablets. 1. Mean +/- S.E. values of Cmax, tmax and AUC0-24 after oral administration of slow-release metoprolol tablets to 75 healthy male volunteers and 15 arrhythmic patients were 95.3 +/- 6.6 ng/ml, 4.4 +/- 0.2 h and 1000.4 +/- 70.9 ng.h/ml, respectively. 2. The number of poor metoprolol metabolizers after the oral administration of slow-release tablets in 75 healthy volunteers and 15 patients was estimated to be 2 subjects (2.2%). 3. The frequency distribution of Cmax values after oral administration of conventional metoprolol tablets was similar to that of slow-release metoprolol tablets. In addition, from the result of this study and that obtained in another study, in which the frequency of poor metoprolol metabolizers in British people has been examined, it is concluded that the frequency of poor metoprolol metabolizers varies between ethnic groups (2.2% in Japanese population and 11.3% in British population.

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