Comparison of two long-acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing.
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.
D000328:Adult; D001262:Atenolol / Q000008:administration & dosage*; D003647:Debrisoquin / Q000378:metabolism; D003692:Delayed-Action Preparations; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000097:blood; D005082:Physical Exertion; D011412:Propanolamines / Q000008:administration & dosage*; D013997:Time Factors
D003692:Delayed-Action Preparations; D011412:Propanolamines; D001262:Atenolol; D008790:Metoprolol; D003647:Debrisoquin