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Cardiovascular Drugs and Therapy

, Volume 3, Issue 4, pp 529–533 | Cite as

Pharmacokinetic and pharmacodynamic comparison of conventional and controlled release formulations of motoprolol in healthy chinese subjects

  • Yuan-Teh Lee
  • Chiau-Suang Liau
  • Ellick C. K. Wong
  • Wen-Jone Chen
  • Mingo-Fong Chen
  • Cueng-Chi Chen
Hypertension

Summary

A double-blind, crossover comparison of the pharmacokinetics and pharmacodynamics of controlled- release metoprolol (CR) 100 mg and 200 mg, metoprolol plain tablet 100 mg, metoprolol Durules 200 mg, and placebo was carried out in 10 healthy Chinese subjects. Standardized treadmill exercise tests according to the Bruce protocol were performed at a steady state of medication, before and 2, 6, 12 and 24 hours after the dose, and multiple blood samples were collected for determination of the metoprolol concentration. The plasma metoprolol levels over 24 hours were more uniform after metoprolol CR than Durules and the plain tablet. The mean peak concentrations for CR 100 mg, 200 mg, Durules, and the plain tablets were 231, 426, 790, and 1105 nmol/l, respectively. The corresponding fluctuation incides were 1.1, 1.5, 2.2, and 5.0. The effects on exercise heart rate (EHR) were investigated at steady state. Metoprolol CR produced more even reduction in EHR over 24 hours than Durules and plain tablets. All four treatments gave similar maximal reduction in EHR of about 20% at 2 hours after the dose. In conclusion, once daily metoprolol CR showed almost even blood levels and provided relatively constant levels of beta1 blockade over 24 hours in healthy Chinese subjects.

Key Words

metoprolol controlled-release formulation conventional tablet plasma concentration exercise heart rate 

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References

  1. 1.
    Olsson G, Rehnqvist N, Sjogren A, et al. Long term treatment with metoprolol after myocardial infarction: Effect on 3 year mortality and morbidity.J Am Coll Cardiol 1985; 5(6):1428–1437.PubMedGoogle Scholar
  2. 2.
    Olsson G, Lubsen J, van Es G-A, et al. Quality of life after myocardial infarction: Effect of long-term metoprolol on mortality and morbidity.Br Med J 1985; 292:1491–1493.Google Scholar
  3. 3.
    Wikstrand J, Warnold I, Olsson G, et al. Primary prevention with metoprolol in patients with hypertension—mortality results from the MAPHY study.JAMA 1988; 259:1976–1982.PubMedGoogle Scholar
  4. 4.
    Sandberg A, Ragnarsson G, Jonsson UE, et al. Design of a new multiple-unit controlled-release formulation of metoprolol—metoprolol CR.Eur J Clin Pharmacol 1988; 33 (Suppl):S3–S7.PubMedGoogle Scholar
  5. 5.
    Oosterhuis B, Jonkman JHG, Kerkhof FA. 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–S18.PubMedGoogle Scholar
  6. 6.
    Blomqvist I, Westergren G, Sandberg A, et al. Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: A comparison with atenolol.Eur J Clin Pharmacol 1988; 33 (Suppl):S19–S24.PubMedGoogle Scholar
  7. 7.
    Sandberg A, Blomqvist I, Jonsson UE, et al. 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–S14.PubMedGoogle Scholar
  8. 8.
    Bruce RA, Kusumi F, Hosmer D. Maximal oxygen intake and normographic assessment of functional aerobic impairment in cardiovascular disease.Am Heart J 1973; 85:546–562.PubMedGoogle Scholar
  9. 9.
    Ervik M, Kylberg-Hanssen K, Johansson L. Determination of metoprolol in plasma and urine using high-resolution gas- chromatography and electron-capture detection.J Chromatogr 1986; 381:168–174.PubMedGoogle Scholar
  10. 10.
    Skelly JP, Barr WH. Biopharmaceutic considerations in designing and evaluating novel drug delivery systems.Clin Res Pract Drug Reg Affairs 1985; 3:501–539.Google Scholar
  11. 11.
    Freestone S, Silas JH, Lennard MS, et al. Comparison of two long-acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing.Br J Clin Pharmacol 1982; 14:713–718.PubMedGoogle Scholar
  12. 12.
    Johnsson G, Jordo L, Lundberg P, et al. Plasma levels and pharmacological effects of metoprolol administered as controlled release (Durules) and ordinary tablets in healthy volunteers.Int J Clin Pharm Ther Toxicol 1980; 18:292–297.Google Scholar
  13. 13.
    Kendell MJ, John VA, Quarterman CP, et al. A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metoprolol.Eur J Clin Pharmacol 1980; 17:87–92.PubMedGoogle Scholar
  14. 14.
    Johansson SR, McCall M, Wilhelmsson C, et al. Duration of action of beta blockers.Clin Pharmacol Ther 1980; 27:593–601.PubMedGoogle Scholar
  15. 15.
    Muller JE, Stone PH, Turi ZG, et al. Circadian variation in the frequency of onset of acute myocardial infarction.N Eng J Med 1985; 313:1315–1322Google Scholar
  16. 16.
    Houtzagers JJR, Smilde JG, Creytens, G, et al. 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–S44.PubMedGoogle Scholar
  17. 17.
    Egstrup K, Gundersen T, Harkonen R, et al. 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–S49.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Yuan-Teh Lee
    • 1
  • Chiau-Suang Liau
    • 1
  • Ellick C. K. Wong
    • 2
  • Wen-Jone Chen
    • 1
  • Mingo-Fong Chen
    • 1
  • Cueng-Chi Chen
    • 1
  1. 1.Department of Medicine (Cardiology)National Taiwan UniversityTaipeiTaiwan
  2. 2.Astra Asia Regional OfficeSingapore

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