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Clinical Pharmacokinetics

, Volume 37, Supplement 1, pp 1–6 | Cite as

Current Status of Sustained Release Formulations in the Treatment of Hypertension

An Overview
  • Ernst Mutschler
  • Heinrich Knauf
Review Article

Abstract

The principal advantages to be gained from controlling the variables of drug release in sustained release formulations are as follows: (i) a more uniform plasma drug profile with fewer occasions when super- or subtherapeutic concentrations of the drug, or its active metabolite(s), occur; and (ii) a smoother therapeutic response over the dosage interval (provided the time-course of drug effects reflects the plasma concentration-time profile). Clinically, this offers the potential to optimise drug therapy and decrease the occurrence of concentration-related adverse effects. In addition, sustained release formulations may increase the likelihood of patient acceptance of therapy, and a once-daily sustained release formulation of a shorter-acting drug that provides a ‘residual’ therapeutic response at the end of the dosage interval can provide additional ‘cover’ in comparison with a once-daily conventional (immediate release) formulation.

In the treatment of hypertension, there are potential advantages to be gained from continuous 24-hour control of blood pressure (BP), particularly in view of epidemiological evidence linking the apparent underperformance of antihypertensive therapy in some major intervention trials in reducing the occurrence of coronary heart disease to predicted levels with a relative failure to control diurnal BP fluctuations. In this regard, the concept of the trough: peak ratio as a measure of antihypertensive efficacy has gained increasing acceptance during recent years. A sustained release antihypertensive formulation offering an improved plasma concentration-time profile and an adequately high trough: peak ratio may therefore provide more consistent 24-hour BP-lowering activity, with attenuation of early morning BP surges and maximal target organ protection. This, coupled with the fact that sustained release formulations can also provide economic advantages in cardiovascular therapeutics by lowering overall health expenditure (which more than offsets their usually higher acquisition costs in comparison with immediate release formulations), suggests that they may have an increasingly important role to play in the future.

Keywords

Adis International Limited Sustained Release Indapamide Peak Ratio Antihypertensive Efficacy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Hansson L. The benefits of lowering elevated blood pressure: a critical review of studies of cardiovascular morbidity and mortality in hypertension. J Hypertens 1996; 14: 537–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Hansson L. Success in the treatment of hypertension: a status report. J Hypertens 1997; 15 Suppl. 2: S11–15.Google Scholar
  3. 3.
    Moser M. Effect of diuretics on morbidity and mortality in the treatment of hypertension. Cardiology 1994; Suppl. 2: 27–35.CrossRefGoogle Scholar
  4. 4.
    Linjer E, Hansson L. Underestimation of the true benefits of antihypertensive treatment: assessment of some important sources of error. J Hypertens 1997; 15: 221–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Meredith PA. Role of trough to peak efficacy in the evaluation of antihypertensive efficacy. J Hypertens 1998; 16 Suppl. 1: S59–64.Google Scholar
  6. 6.
    Mancia G, Sega R, Milesi C, et al. Blood-pressure control in the hypertensive population. Lancet 1997; 349: 454–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Kellaway IW. Scientific rationale and clinical implications of sustained-release formulations. Br J Clin Pract 1988; 42 Suppl. 60: 9–13.Google Scholar
  8. 8.
    Goldberg Arnold RJ, Kaniecki DJ. Selection of oral controlled-release drugs: a critical decision for the physician. South Med J 1993;86:208–14.CrossRefGoogle Scholar
  9. 9.
    Katz B, Rosenberg A, Frishman WH. Controlled-release drug delivery systems in cardiovascular medicine. Am Heart J 1995; 129: 359–68.PubMedCrossRefGoogle Scholar
  10. 10.
    Colombo P, Bettini R, Peracchia MT, et al. Controlled release dosage forms: from ground to space. Eur J Drug Metab Pharmacokinet 1996; 21: 87–91.PubMedCrossRefGoogle Scholar
  11. 11.
    Chien YW. Rate-control drug delivery systems: controlled release vs. sustained release. Med Prog Technol 1989; 15: 21–46.PubMedGoogle Scholar
  12. 12.
    Read NW, Sugden K. Gastrointestinal dynamics and pharmacology for the optimum design of controlled-release oral dosage forms. Crit Rev Ther Drug Carrier Syst 1988; 4: 221–63.PubMedGoogle Scholar
  13. 13.
    Bataillard A, Schiavi P, Sassard J. Pharmacological properties of indapamide: rationale for use in hypertension. Clin Pharmacokinet 1999; 37 Suppl. 1: 7–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Damien G, Huet de Barochez B, Schiavi P. Galenic development and pharmacokinetic profile of indapamide sustained release 1.5mg. Clin Pharmacokinet 1999; 37 Suppl. 1: 13–19.PubMedCrossRefGoogle Scholar
  15. 15.
    Donnelly R. Clinical implications of indapamide sustained release 1.5mg in hypertension. Clin Pharmacokinet 1999; 37 Suppl. 1:21–32.PubMedCrossRefGoogle Scholar
  16. 16.
    Hansson L. Pursuit of the optimal outcome in hypertension. Clin Pharmacokinet 1999; 37 Suppl. 1: 33–38.PubMedCrossRefGoogle Scholar
  17. 17.
    Steinijans VW. Pharmacokinetic characterization of controlled-release formulations. Eur J Drug Metab Pharmacokinet 1990; 15: 173–81.PubMedCrossRefGoogle Scholar
  18. 18.
    Omboni S, Parati G, Zanchetti A, et al. Calculation of trough-to-peak ratio of antihypertensive treatment from ambulatory blood pressure: methodological aspects. J Hypertens 1995; 13: 1105–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Myers MG. Suggested guidelines for determining the trough-to-peak ratio of antihypertensive drugs. Am J Hypertens 1996; 9: 76S–82S.PubMedGoogle Scholar
  20. 20.
    Mallion J-M, Asmar R, Boutelant S, et al. Twenty-four hour antihypertensive efficacy of indapamide, 1.5-mg sustained release: results of two randomized double-blind controlled studies. J Cardiovasc Pharmacol 1998; 32: 673–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Parati G, Pomidosssi G, Albini F, et al. Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hyertension. J Hypertens 1987; 5: 93–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Meredith PA, Perloff D, Mancia G, et al. Blood pressure variability and its implications for antihypertensive therapy. Blood Press 1995; 4: 5–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Myers MG. Twenty-four-hour blood pressure control: a brief review of aspects of target-organ protection. J Hypertens 1996; 14 Suppl. 6: S7–10.CrossRefGoogle Scholar
  24. 24.
    Schiavi P, Jochemsen R, Hiley M, et al. Pharmacokinetics of slow and immediate release formulations of indapamide after repeated administration, in healthy volunteers. Eur J Drug Metab Pharmacokinet 1996; Special Issue: 41.Google Scholar
  25. 25.
    Elliott HL, Meredith PA. Trough: peak ratio: clinically useful or practically irrelevant? J Hypertens 1995; 13: 279–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Powers Cramer M, Saks SR. Translating safety, efficacy and compliance into economic value for controlled release dosage forms. Pharmacoeconomics 1994; 5: 482–504.CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Ernst Mutschler
    • 1
  • Heinrich Knauf
    • 2
  1. 1.Pharmakologisches Institut für NaturwissenschaftlerJohann Wolfgang Goethe-Universität, Biocentre NiederurselFrankfurt/MainGermany
  2. 2.Medizinische Klinik I, St. Bernward-KrankenhausHildesheimGermany

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