Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1988 May;25(5):539–545. doi: 10.1111/j.1365-2125.1988.tb03343.x

Concentration-effect relationships for oxprenolol in patients with essential hypertension.

G T McInnes 1, M J Brodie 1
PMCID: PMC1386426  PMID: 3408634

Abstract

1. Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following single and repeated doses of oxprenolol administered once daily as oral osmotic drug delivery systems (10/170 and 16/260 oxprenolol OROS). 2. Plasma oxprenolol concentration profiles after each preparation were consistent with the criteria for sustained drug release. Levels immediately after exercise were significantly higher than those prior to exercise (P less than 0.001), but differences were slight. 3. Both OROS drug forms reduced exercise heart rate for 24 h after single and repeated doses; effects were greater for 16/260 OROS than for 10/170 OROS. Significant reductions in post-exercise systolic BP were observed 24 h after drug administration and after repeated doses there was little difference between the preparations. Effects on diastolic BP after exercise were slight. 4. The relationship between plasma oxprenolol concentrations and exercise heart rates fitted an exponential mathematical model which makes allowance for inter-individual variability. No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP.

Full text

PDF
539

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett P. N., Bennett J., Bradbrook I., Francis J., John V. A., Rogers H., Turner P., Warrington S. J. Single-dose pharmacokinetic and pharmacodynamic comparison of polymer-matrix (Slow Trasicor) and Oros dosage forms of oxprenolol in healthy volunteers. Br J Clin Pharmacol. 1985;19 (Suppl 2):171S–175S. doi: 10.1111/j.1365-2125.1985.tb02758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bobik A., Jennings G. L., Korner P. I., Ashley P., Jackman G. Absorption and excretion of rapid and slow release oxprenolol and their effects on heart rate and blood pressure during exercise. Br J Clin Pharmacol. 1979 Jun;7(6):545–549. doi: 10.1111/j.1365-2125.1979.tb04640.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brunner L., Imhof P., Jack D. Relation between plasma concentrations and cardiovascular effects of oral oxprenolol in man. Eur J Clin Pharmacol. 1975;8(1):3–9. doi: 10.1007/BF00616408. [DOI] [PubMed] [Google Scholar]
  4. Chidsey C., Pine M., Favrot L., Smith S., Leonetti G., Morselli P., Zanchetti A. The use of drug concentration measurements in studies of the therapeutic response to propranolol. Postgrad Med J. 1976;52 (Suppl 4):26–32. [PubMed] [Google Scholar]
  5. Collste P., Haglund K., Frisk-Holmberg M., Orme M. L., Rawlins M. D., Ostman J. Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. II. Relationship to its effect on blood pressure and plasma renin activity. Eur J Clin Pharmacol. 1976 Jun 15;10(2):89–95. doi: 10.1007/BF00609465. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Esler M., Zweifler A., Randall O., DeQuattro V. Pathophysiologic and pharmacokinetic determinants of the antihypertensive response to propranolol. Clin Pharmacol Ther. 1977 Sep;22(3):299–308. doi: 10.1002/cpt1977223299. [DOI] [PubMed] [Google Scholar]
  8. Frishman W., Silverman R. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 2. Physiologic and metabolic effects. Am Heart J. 1979 Jun;97(6):797–807. doi: 10.1016/0002-8703(79)90016-4. [DOI] [PubMed] [Google Scholar]
  9. Holford N. H., Sheiner L. B. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet. 1981 Nov-Dec;6(6):429–453. doi: 10.2165/00003088-198106060-00002. [DOI] [PubMed] [Google Scholar]
  10. Hurwitz G. A., Webb J. G., Walle T., Bai S. A., Daniell H. B., Gourley L., Boyd Loadholt C., Gaffney T. E. Exercise-induced increments in plasma levels of propranolol and noradrenaline. Br J Clin Pharmacol. 1983 Dec;16(6):599–608. doi: 10.1111/j.1365-2125.1983.tb02228.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Israili Z. H. Correlation of pharmacological effects with plasma levels of antihypertensive drugs in man. Annu Rev Pharmacol Toxicol. 1979;19:25–52. doi: 10.1146/annurev.pa.19.040179.000325. [DOI] [PubMed] [Google Scholar]
  12. Leenen F. H., Coenen C. H., Zonderland M., Maas A. H. Effects of cardioselective and nonselective beta-blockade on dynamic exercise performance in mildly hypertensive men. Clin Pharmacol Ther. 1980 Jul;28(1):12–21. doi: 10.1038/clpt.1980.124. [DOI] [PubMed] [Google Scholar]
  13. Martin M. A., Phillips F. C., Tucker G. T., Smith A. J. Acebutolol in hypertension: relationships between drug concentration and effects. Eur J Clin Pharmacol. 1978 Dec 18;14(6):383–390. doi: 10.1007/BF00716378. [DOI] [PubMed] [Google Scholar]
  14. Mason W. D., Winer N. Pharmacokinetics of oxprenolol in normal subjects. Clin Pharmacol Ther. 1976 Oct;20(4):401–412. doi: 10.1002/cpt1976204401. [DOI] [PubMed] [Google Scholar]
  15. McAinsh J., Baber N. S., Smith R., Young J. Pharmacokinetic and pharmacodynamic studies with long-acting propranolol. Br J Clin Pharmacol. 1978 Aug;6(2):115–121. doi: 10.1111/j.1365-2125.1978.tb00835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McDevitt D. G., Shand D. G. Plasma concentrations and the time-course of beta blockade due to propranolol. Clin Pharmacol Ther. 1975 Dec;18(6):708–713. doi: 10.1002/cpt1975186708. [DOI] [PubMed] [Google Scholar]
  17. McDevitt D. G. The assessment of beta-adrenoceptor blocking drugs in man. Br J Clin Pharmacol. 1977 Aug;4(4):413–425. doi: 10.1111/j.1365-2125.1977.tb00756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Petrie J. C., Jeffers T. A., Robb O. J., Scott A. K., Webster J. Atenolol, sustained-release oxprenolol, and long-acting propranolol in hypertension. Br Med J. 1980 Jun 28;280(6231):1573–1574. doi: 10.1136/bmj.280.6231.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Powis G., Snow D. H. The effects of exercise and adrenaline infusion upon the blood levels of propranolol and antipyrine in the horse. J Pharmacol Exp Ther. 1978 Jun;205(3):725–731. [PubMed] [Google Scholar]
  20. Racine-Poon A., Moppert J. Concentration-effect relationship of oxprenolol in healthy volunteers: a retrospective analysis. Br J Clin Pharmacol. 1985;19 (Suppl 2):143S–149S. doi: 10.1111/j.1365-2125.1985.tb02755.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Robinson B. F., Epstein S. E., Beiser G. D., Braunwald E. Control of heart rate by the autonomic nervous system. Studies in man on the interrelation between baroreceptor mechanisms and exercise. Circ Res. 1966 Aug;19(2):400–411. doi: 10.1161/01.res.19.2.400. [DOI] [PubMed] [Google Scholar]
  22. Silke B., John V. A., Calvert R. T., Taylor S. H. Initiation and maintenance of beta-blockade with intravenous oxprenolol. Eur J Clin Pharmacol. 1983;24(1):7–14. doi: 10.1007/BF00613920. [DOI] [PubMed] [Google Scholar]
  23. Theeuwes F. Elementary osmotic pump. J Pharm Sci. 1975 Dec;64(12):1987–1991. doi: 10.1002/jps.2600641218. [DOI] [PubMed] [Google Scholar]
  24. Theeuwes F., Swanson D. R., Guittard G., Ayer A., Khanna S. Osmotic delivery systems for the beta-adrenoceptor antagonists metoprolol and oxprenolol: design and evaluation of systems for once-daily administration. Br J Clin Pharmacol. 1985;19 (Suppl 2):69S–76S. doi: 10.1111/j.1365-2125.1985.tb02745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wilson M., Morgan G., Morgan T. The effect on blood pressure of beta-adrenoceptor blocking drugs administered once daily and their duration of action when therapy is ceased. Br J Clin Pharmacol. 1976 Oct;3(5):857–861. doi: 10.1111/j.1365-2125.1976.tb00638.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES