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PMID: 1773547 Published · ppublish English Journal Article Review

Controlled release metoprolol. Clinical pharmacokinetic and therapeutic implications.

Clinical pharmacokinetics ·Vol. 21 ·No. 5 ·1991-11-00 ·Pages 319-30

Kendall MJ, Maxwell SR, Sandberg A, Westergren G

Abstract

Metoprolol is a relatively beta 1-selective beta-blocker used extensively to treat hypertension and angina and as a prophylaxis after myocardial infarction. Conventional formulations are usually administered twice daily and the drug has a tendency to lose its selectivity of action at higher plasma concentrations. Two controlled release formulations, metoprolol CR and metoprolol 'Oros', have made it possible to achieve sustained beta 1-blockade over an entire 24h period and to minimise the loss of selectivity associated with higher plasma concentrations. The CR formulation has been extensively investigated and is the major subject of this review. The 'Oros' formulation is pharmaceutically different from the CR, yet both produce similar plasma concentration profiles and comparable beta 1-blocking effects. The availability of these preparations occurs at a time when increasingly persuasive data are becoming available on the cardioprotective or coronary preventive action of metoprolol.

MeSH Terms
Biological Availability Delayed-Action Preparations Hemodynamics/drug effects Humans Hypertension/drug therapy Metoprolol/pharmacokinetics,pharmacology
Chemicals
Delayed-Action Preparations Metoprolol
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kendall M J
Department of Medicine, Queen Elizabeth Hospital, Birmingham, England.
Maxwell S R
Sandberg A
Westergren G
References (65)
65 references, click to expand
  1. Can the biochemical responses to a beta 2-adrenoceptor stimulant be used to assess the selectivity of beta-adrenoceptor blockers?
    Br J Clin Pharmacol. 1983 Nov;16(5):557-60 PMID: 6139123
  2. Effect of controlled-release metoprolol on blood pressure and exercise heart rate in hypertension: a comparison with conventional tablets.
    Eur J Clin Pharmacol. 1988;33 Suppl:S33-7 PMID: 3371392
  3. Effect of metoprolol on diet-induced atherosclerosis in rabbits.
    Arteriosclerosis. 1988 Jan-Feb;8(1):40-5 PMID: 3341991
  4. Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study.
    JAMA. 1988 Apr 1;259(13):1976-82 PMID: 3346979
  5. Elementary osmotic pump.
    J Pharm Sci. 1975 Dec;64(12):1987-91 PMID: 1510
  6. Beta-blockers and cardioprotection--is there any good news from the recent trials?
    J Clin Pharm Ther. 1987 Dec;12(6):347-50 PMID: 3326884
  7. Primary prevention with beta-blockade in patients with hypertension: review of results and clinical implications.
    J Cardiovasc Pharmacol. 1990;16 Suppl 5:S64-75 PMID: 11527139
  8. Is metoprolol CR/ZOK more selective than conventional metoprolol and atenolol?
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S98-102 PMID: 2155948
  9. Comparative evaluation of cardioselectivity of metoprolol OROS and atenolol: a double-blind, placebo-controlled crossover study.
    Am Heart J. 1990 Aug;120(2):467-72 PMID: 2200257
  10. Comparison of beta adrenergic receptor subtypes in mammalian tissues.
    J Pharmacol Exp Ther. 1979 Dec;211(3):502-8 PMID: 229209
  11. Metoprolol in acute myocardial infarction (MIAMI). A randomised placebo-controlled international trial. The MIAMI Trial Research Group.
    Eur Heart J. 1985 Mar;6(3):199-226 PMID: 2863148
  12. Design of a new multiple-unit controlled-release formulation of metoprolol--metoprolol CR.
    Eur J Clin Pharmacol. 1988;33 Suppl:S3-7 PMID: 3371391
  13. Antihypertensive treatment with metoprolol or hydrochlorothiazide in patients aged 60 to 75 years. Report from a double-blind international multicenter study.
    JAMA. 1986 Mar 14;255(10):1304-10 PMID: 3511308
  14. The effects of beta-adrenergic blocking agents on atherosclerosis and its complications.
    Eur Heart J. 1987 Sep;8(9):928-44 PMID: 2889599
  15. The antianginal efficacy and tolerability of controlled-release metoprolol once daily: a comparison with conventional metoprolol tablets twice daily.
    Eur J Clin Pharmacol. 1988;33 Suppl:S45-9 PMID: 3371394
  16. Long-term treatment with metoprolol after myocardial infarction: effect on 3 year mortality and morbidity.
    J Am Coll Cardiol. 1985 Jun;5(6):1428-37 PMID: 3889100
  17. The relationship between metoprolol plasma concentration and beta 1-blockade in healthy subjects: a study on conventional metoprolol and metoprolol CR/ZOK formulations.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S46-54 PMID: 1968913
  18. Beta-adrenoceptor blocking drugs: adverse reactions and drug interactions.
    Pharmacol Ther. 1983;21(3):351-69 PMID: 6138787
  19. The role of clinical pharmacology in the development and evaluation of oral controlled-release dosage forms.
    Br J Clin Pharmacol. 1985;19 Suppl 2:65S-67S PMID: 2860917
  20. Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population.
    Am J Cardiol. 1987 Oct 1;60(10):801-6 PMID: 3661393
  21. The polymorphic oxidation of beta-adrenoceptor antagonists. Clinical pharmacokinetic considerations.
    Clin Pharmacokinet. 1986 Jan-Feb;11(1):1-17 PMID: 2868819
  22. Beta adrenoceptor blockade is associated with increased survival in male but not female hypertensive patients: a report from the DHSS Hypertension Care Computing Project (DHCCP).
    J Hum Hypertens. 1988 Dec;2(4):219-27 PMID: 2907053
  23. Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders.
    Drugs. 1986 May;31(5):376-429 PMID: 2940080
  24. Efficacy and tolerability of a new controlled-release formulation of metoprolol: a comparison with conventional metoprolol tablets in mild to moderate hypertension.
    Eur J Clin Pharmacol. 1988;33 Suppl:S39-44 PMID: 3371393
  25. Pharmacokinetic and pharmacodynamic properties of metoprolol in patients with impaired renal function.
    Clin Pharmacokinet. 1980 Mar-Apr;5(2):169-80 PMID: 6102500
  26. A dose-response study on metoprolol in angina pectoris.
    Ann Clin Res. 1981;13 Suppl 30:54-7 PMID: 7027894
  27. Beta-adrenoceptor-blocking drugs and blood sugar control in diabetes mellitus.
    Br Med J. 1979 Jan 20;1(6157):159-61 PMID: 369646
  28. Increased cardiac output and lowered peripheral resistance during metoprolol treatment.
    Acta Med Scand Suppl. 1983;672:105-10 PMID: 6579824
  29. Plasma levels and pharmacological effects of metoprolol administered as controlled release (Durules) and ordinary tablets in healthy volunteers.
    Int J Clin Pharmacol Ther Toxicol. 1980 Jul;18(7):292-7 PMID: 7000717
  30. Cardiovascular and renal effects of long-term antihypertensive treatment.
    JAMA. 1988 May 6;259(17):2553-7 PMID: 3357228
  31. Pharmacokinetic and pharmacodynamic comparison of a new controlled-release formulation of metoprolol with a traditional slow-release formulation.
    Eur J Clin Pharmacol. 1988;33 Suppl:S15-8 PMID: 3371389
  32. Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: a comparison with atenolol.
    Eur J Clin Pharmacol. 1988;33 Suppl:S19-24 PMID: 3371390
  33. Oxidation phenotype--a major determinant of metoprolol metabolism and response.
    N Engl J Med. 1982 Dec 16;307(25):1558-60 PMID: 7144837
  34. Early intravenous beta-blockade in acute myocardial infarction.
    Cardiology. 1989;76(2):132-43 PMID: 2568179
  35. Pharmacokinetic studies on the selective beta1-receptor antagonist metoprolol in man.
    J Pharmacokinet Biopharm. 1974 Aug;2(4):347-64 PMID: 4155762
  36. Investigation of drug absorption from the gastrointestinal tract of man. III. Metoprolol in the colon.
    Br J Clin Pharmacol. 1985;19 Suppl 2:113S-118S PMID: 4005112
  37. Circadian variation in the frequency of onset of acute myocardial infarction.
    N Engl J Med. 1985 Nov 21;313(21):1315-22 PMID: 2865677
  38. A comparison of a controlled release (CR/ZOK) formulation of metoprolol, once daily, with conventional metoprolol tablets, twice daily, in mild to moderate hypertension.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S61-5 PMID: 2179282
  39. Beta blockers and fatigue.
    J Clin Hosp Pharm. 1984 Dec;9(4):283-91 PMID: 6151954
  40. Influence of metoprolol CR/ZOK on plasminogen activator inhibitor (PAI-1) in man: a pilot study.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S132-7 PMID: 2312774
  41. 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 PMID: 7371709
  42. Controlled-release metoprolol compared with atenolol in asthmatic patients: interaction with terbutaline.
    Eur J Clin Pharmacol. 1988;33 Suppl:S25-32 PMID: 2836204
  43. A double-blind trial of metoprolol in acute myocardial infarction. Effects on ventricular tachyarrhythmias.
    N Engl J Med. 1983 Mar 17;308(11):614-8 PMID: 6828092
  44. The efficacy of low dose metoprolol CR/ZOK in mild hypertension and in elderly patients with mild to moderate hypertension.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S66-71 PMID: 2179283
  45. Pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK once daily with conventional tablets once daily and in divided doses.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S17-27 PMID: 2312775
  46. Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S2-16 PMID: 2179280
  47. Effect of short-term beta blockade on serum lipid levels and on the interaction of LDL with human arterial proteoglycans.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S124-31 PMID: 2107215
  48. Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers.
    Clin Pharmacol Ther. 1983 Dec;34(6):732-7 PMID: 6641087
  49. Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.
    Circulation. 1990 Sep;82(3):941-50 PMID: 1975521
  50. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction.
    N Engl J Med. 1981 Apr 2;304(14 ):801-7 PMID: 7010157
  51. Comparison of two slow-release formulations of metoprolol with conventional metoprolol and atenolol in hypertensive patients.
    Br J Clin Pharmacol. 1985 Oct;20(4):387-91 PMID: 4074607
  52. A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results.
    JAMA. 1982 Mar 26;247(12):1707-14 PMID: 7038157
  53. A pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK with a conventional slow release preparation.
    J Clin Pharmacol. 1990 Feb;30(2 Suppl):S33-8 PMID: 2312777
  54. Subjective symptoms and pharmacokinetics/dynamics of metoprolol CR in elderly subjects--a comparison with atenolol.
    Eur J Clin Pharmacol. 1990;38(6):571-8 PMID: 2373131
  55. Effect of inflammatory disease on plasma concentrations of three beta-adrenoceptor blocking agents.
    Int J Clin Pharmacol Ther Toxicol. 1981 Apr;19(4):158-62 PMID: 6114930
  56. Beta blockade during and after myocardial infarction: an overview of the randomized trials.
    Prog Cardiovasc Dis. 1985 Mar-Apr;27(5):335-71 PMID: 2858114
  57. Confusing messages from the newest of the beta-blocker/diuretic hypertension trials. The Metoprolol Atherosclerosis Prevention in Hypertensives trial.
    Arch Intern Med. 1989 Oct;149(10):2174-5 PMID: 2572204
  58. Reduction of nonfatal reinfarctions in patients with a history of hypertension by chronic postinfarction treatment with metoprolol.
    Acta Med Scand. 1986;220(1):33-8 PMID: 3532695
  59. The effect of age on the pharmacokinetics of metoprolol and its metabolites.
    Br J Clin Pharmacol. 1981 Mar;11(3):287-94 PMID: 7213530
  60. The role of sympathetic activity in atherogenesis: effects of beta-blockade.
    Am Heart J. 1988 Jul;116(1 Pt 2):322-7 PMID: 2899391
  61. Effect on mortality of metoprolol in acute myocardial infarction. A double-blind randomised trial.
    Lancet. 1981 Oct 17;2(8251):823-7 PMID: 6116950
  62. Circadian variation in the frequency of sudden cardiac death.
    Circulation. 1987 Jan;75(1):131-8 PMID: 3791599
  63. Propranolol increases prostacyclin synthesis in patients with essential hypertension.
    Hypertension. 1988 Dec;12(6):582-8 PMID: 3060430
  64. Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets.
    Eur J Clin Pharmacol. 1988;33 Suppl:S9-14 PMID: 3371395
  65. Beta-blockers and primary prevention of coronary heart disease in patients with high blood pressure.
    JAMA. 1989 Apr 14;261(14):2087-94 PMID: 2564445
Article Info
Journal
Clinical pharmacokinetics
Abbr.
Clin Pharmacokinet
ISSN
0312-5963
DOI
10.2165/00003088-199121050-00001
Published
1991-11-00
Pages
319-30
Language
English
Region
Switzerland
NLM ID
7606849
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.2165/00003088-199121050-00001 View journal details
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