Clinical Pharmacokinetics

, Volume 24, Issue 1, pp 59–70 | Cite as

Optimising ACE Inhibitor Therapy of Congestive Heart Failure

Insights from Pharmacodynamic Studies
  • Robert J. Cody
Review Article Pharmacokinetic Pharmacodynamic Relationships


Pharmacokinetic studies are often used to provide additional information regarding the use of pharmacological agents for the treatment of cardiovascular disorders. Pharmacokinetic data are available for the major angiotensin converting enzyme (ACE) inhibitors. However, practical guidelines regarding dosage and dosage intervals are not feasible, and measurements of serum drug concentrations are generally not useful in practice. Such use is obscured by the nature of enzymatic inhibition, renin and angiotensin I accumulation, the complex interaction of several organ systems, the compromise of organ system function due to the heart failure process, the effect of ACE inhibitors on other vasoactive substances and the cellular actions of carboxypeptidase (the enzyme otherwise known as ACE). Pharmacodynamic data demonstrate 2 important factors that influence ACE inhibitor pharmacokinetics and serum concentrations: the aging process and abnormal renal function. As most patients with moderate to severe heart failure have reduced renal function, this has practical implications. Furthermore, heart failure is common in the elderly, and even within the population with heart failure, a superimposed further reduction in renal function can be identified in elderly patients with heart failure.

Therefore, a more careful analysis of ACE inhibitor dosage must be made in the presence of decreased renal function and in the elderly patient with heart failure.


Renin Angiotensin Converting Enzyme Captopril Enalapril Lisinopril 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Biollaz J, Burnier M, Turini GA, Brunner DB, Porchet M, et al. Three new long-acting converting enzyme inhibitors: relationship between plasma converting enzyme activity and response to angiotensin I. Clinical Pharmacology and Therapeutics 29: 665–670, 1981PubMedCrossRefGoogle Scholar
  2. Cody RJ. Hemodynamic responses to specific renin angiotensin inhibitors in hypertension and heart failure: a review. Drugs 28: 144–169, 1984PubMedCrossRefGoogle Scholar
  3. Cody RJ. Clinical and hemodynamic experience with enalapril in congestive heart failure. American Journal of Cardiology 55: 36A–40A, 1985PubMedCrossRefGoogle Scholar
  4. Cody RJ. Renin system inhibition: beginning the fourth epoch. Circulation 85: 362–364, 1992PubMedCrossRefGoogle Scholar
  5. Cody RJ, Covit AB, Schaer GL, Laragh JH. Evaluation of a long-acting converting enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure. Journal of the American College of Cardiology 1: 1154–1159, 1983PubMedCrossRefGoogle Scholar
  6. Cody RJ, Laragh JH. The renin-angiotensin-aldosterone system in chronic congestive heart failure: pathophysiology and implications for treatment. In Cohn (Ed.) Drug treatment of heart failure: advanced therapeutics communications, pp. 79–104, advanced Therapeutics Communications, Secaucus, 1988Google Scholar
  7. Cody RJ, Ljungman S, Covit AB, Kubo SH, Sealey JE, et al. Regulation of glomerular filtration rate in chronic congestive heart failure patients. Kidney International 34: 361–367, 1988PubMedCrossRefGoogle Scholar
  8. Cody RJ, Schaer FL, Covit AB, Pondolfino K, Williams G. Captopril kinetics in chronic congestive heart failure. Clinical Pharmacology and Therapeutics 32: 721–726, 1982PubMedCrossRefGoogle Scholar
  9. Cody RJ, Torre S, Clark M, Pondolfino K. Age-related hemodynamic, renal, and hormonal differences in patients with congestive heart failure. Archives of Internal Medicine 149: 1023–1028, 1989PubMedCrossRefGoogle Scholar
  10. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. New England Journal of Medicine 316: 1425–1435, 1987CrossRefGoogle Scholar
  11. Cushman DW, Wang FL, Fung WC, Harvey CM, DeForrest JM. Differentiation of angiotensin converting enzyme (ACE) inhibitors by their selective inhibition of ACE in physiologically important target organs. American Journal of Hypertension 2: 294–306, 1989PubMedGoogle Scholar
  12. Dickstein K. Hemodynamic, hormonal and pharmacokinetic aspects of treatment with lisinopril in congestive heart failure. Journal of Cardiovascular Pharmacology 9 (Suppl. 3): S73–S81, 1987PubMedCrossRefGoogle Scholar
  13. Giles TD, Katz R, Sullivan JM, Worfson P, Haugland M, et al. Short and long-acting angiotensin converting enzyme inhibitors: a randomized trial of lisinopril versus Captopril in the treatment of congestive heart failure. Journal of the American College of Cardiology 13: 1240–1247, 1989PubMedCrossRefGoogle Scholar
  14. Gomez HJ, Cirillo VJ, Moncloa F. The clinical pharmacology of lisinopril. Journal of Cardiovascular Pharmacology 9 (Suppl. 3): S27–S34, 1987PubMedCrossRefGoogle Scholar
  15. Kubo SH, Cody RJ. Clinical pharmacokinetics of angiotensin converting enzyme inhibitors: a review. Clinical Pharmacokinetics 10: 377–391, 1985PubMedCrossRefGoogle Scholar
  16. Kubo SH, Cody RJ, Laragh JH, Prida XE, Atlas S, et al. Immediate converting enzyme inhibition with intravenous enalapril in chronic congestive heart failure. American Journal of Cardiology 55: 122–126, 1985PubMedCrossRefGoogle Scholar
  17. Lancaster SG, Todd PA. Lisinopril: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs 35: 646–669, 1988PubMedCrossRefGoogle Scholar
  18. Packer M, Lee WH, Yushak M, Medina N. Comparison of Captopril and enalapril in patients with severe congestive heart failure. New England Journal of Medicine 315: 847–853, 1986PubMedCrossRefGoogle Scholar
  19. Romankiewicz JA, Brogdan RN, Heel RC, Speight TM, Avery GS. Captopril: an updated review of its pharmacological properties and therapeutic efficacy in congestive heart failure. Drugs 25: 6–40, 1985CrossRefGoogle Scholar
  20. Schwartz JB, Taylor A, Abernathy D, O’Meara M, Farmer J, et al. Pharmacokinetics and pharmacodynamics of enalapril in patients with congestive heart failure and patients with hypertension. Journal of Cardiovascular Pharmacology 7: 767–776, 1985PubMedCrossRefGoogle Scholar
  21. Thompson A, Kelly JG, Whiting B. Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension. British Journal of Clinical Pharmacology 27: 57–65, 1989CrossRefGoogle Scholar
  22. Todd PA, Heel RC. Enalapril: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension and congestive heart failure. Drugs 31: 198–248, 1986PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • Robert J. Cody
    • 1
  1. 1.Division of Cardiology, Department of MedicineThe Ohio State University, College of Medicine and HospitalsColumbusUSA

Personalised recommendations