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Comparison of two long‐acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing.
Author(s) -
Freestone S.,
Silas JH,
Lennard MS,
Ramsay LE
Publication year - 1982
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1982.tb04962.x
Subject(s) - metoprolol , atenolol , medicine , bioavailability , dosing , pharmacology , chemistry , blood pressure
1 Eight healthy men received two long‐acting formulations of metoprolol 200 mg (SA Astra, SR Geigy), conventional metoprolol 200 mg and atenolol 100 mg once daily for 1 week each in balanced, crossover fashion. There was a washout period of at least a week between each phase. 2 On the last day of each phase, post‐exercise heart rate was recorded at intervals and compared to pretreatment values. Plasma metoprolol concentrations were measured. 3 The mean AUC was similar after each of the three formulations of metoprolol (relative bioavailability of SA and SR v conventional was 97%) but with SA and SR metoprolol the time to peak was significantly delayed by about 2 h. 4 In comparison to conventional metoprolol only metoprolol SA was associated with significantly higher plasma metoprolol concentrations at the end of a dosing interval (mean values: conventional, 25 ng/ml, SR 37 ng/ml, SA 51 ng/ml). 5 Mean (+/‐ s.d.) reduction in exercise tachycardia at the end of a dosing interval was significantly greater with atenolol (14.8 +/‐ 4.5%) and metoprolol SA (13.7 +/‐ 10.3%) than with metoprolol SR (10 +/‐ 8.4%) and conventional metoprolol (8.2 +/‐ 7.1%). 6 The variability in beta‐adrenoceptor blockade at 24 h was much greater with each of the three metoprolol formulations than that with atenolol. This was explained by the variability in metoprolol metabolism. 7 Oxidation phenotype testing with debrisoquine showed there were six extensive metabolisers and two poor metabolisers. The AUC, half‐life and response to metoprolol at 24 h were much greater in poor metabolisers. Response to atenolol was not influenced by phenotype.