Abstract
1 Plasma metoprolol concentrations and haemodynamic effects have been measured in six healthy male volunteers during once daily dosing with a 19/285 Oros system and twice daily dosing with 100 mg conventional tablets, on two separate occasions.
2 Plasma drug concentrations throughout the day varied less with the Oros than with the conventional tablet regimen. Predosing concentrations were also higher with Oros but areas under the curve, after correcting for the differences in dose, were similar for the two preparations.
3 Inhibition of exercise tachycardia was drug concentration dependent and was smoothly controlled through the day only with the Oros preparation. Predosing effects at steady-state were also greater for the Oros regimen. The decline in mean blood pressure, however, showed the same daily pattern for both regimens, and no significant differences were detected between Oros and conventional tablet treatments.
4 The smoothness of the plasma profiles after Oros confirmed the controlled-release performance of the system in vivo and indicates its potential in the treatment of angina, cardiac arrhythmias and wherever it is important not to jeopardize steady selective β-adrenoceptor blockade.
Keywords: metoprolol, 19/285 Oros formulation, pharmacokinetics, haemodynamics
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aarons R. D., Nies A. S., Gal J., Hegstrand L. R., Molinoff P. B. Elevation of beta-adrenergic receptor density in human lymphocytes after propranolol administration. J Clin Invest. 1980 May;65(5):949–957. doi: 10.1172/JCI109781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Degen P. H., Riess W. Simplified method for the determination of oxprenolol and other beta-receptor-blocking agents in biological fluids by gas-liquid chromatography. J Chromatogr. 1976 Jun 9;121(1):72–75. doi: 10.1016/s0021-9673(00)82299-2. [DOI] [PubMed] [Google Scholar]
- Freestone S., Silas J. H., Lennard M. S., Ramsay L. E. Comparison of two long-acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing. Br J Clin Pharmacol. 1982 Nov;14(5):713–718. doi: 10.1111/j.1365-2125.1982.tb04962.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kendall M. J., Jack D. B., Woods K. L., Laugher S. J., Quarterman C. P., John V. A. Comparison of the pharmacodynamic and pharmacokinetic profiles of single and multiple doses of a commercial slow-release metoprolol formulation with a new Oros delivery system. Br J Clin Pharmacol. 1982 Mar;13(3):393–398. doi: 10.1111/j.1365-2125.1982.tb01391.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kendall M. J., John V. A., Quarterman C. P., Welling P. G. A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metroprolol. Eur J Clin Pharmacol. 1980 Feb;17(2):87–92. doi: 10.1007/BF00562615. [DOI] [PubMed] [Google Scholar]
- McLean A. J., McNamara P. J., duSouich P., Gibaldi M., Lalka D. Food, splanchnic blood flow, and bioavailability of drugs subject to first-pass metabolism. Clin Pharmacol Ther. 1978 Jul;24(1):5–10. doi: 10.1002/cpt19782415. [DOI] [PubMed] [Google Scholar]
- Melander A., Danielson K., Scherstén B., Wåhlin E. Enhancement of the bioavailability of propranolol and metoprolol by food. Clin Pharmacol Ther. 1977 Jul;22(1):108–112. doi: 10.1002/cpt1977221108. [DOI] [PubMed] [Google Scholar]
- Nattel S., Rangno R. E., Van Loon G. Mechanism of propranolol withdrawal phenomena. Circulation. 1979 Jun;59(6):1158–1164. doi: 10.1161/01.cir.59.6.1158. [DOI] [PubMed] [Google Scholar]
- Nievel J. G., Harvard C. W. A double-blind crossover comparative study of the efficacy of single daily doses of conventional and slow-release metoprolol. Curr Med Res Opin. 1981;7(8):503–515. doi: 10.1185/03007998109112365. [DOI] [PubMed] [Google Scholar]