Advertisement

Prodrugs pp 1251-1258 | Cite as

Case Study: Fosinopril

  • Edward W. Petrillo
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume V)

Abstract

Fosinopril is an acyloxyalkyl ester of fosinoprilat, a phosphinic acid angiotensin-converting enzyme (ACE) inhibitor developed for the treatment of hypertension and congestive heart failure. The hydroxylphosphinylacetyl proline class of inhibitors exhibits high affinity for ACE and a high degree of efficacy for inhibition of the angiotensin I-induced pressor response in animals (Krapcho et al., 1988) when administered intravenously. These inhibitors exhibited a low level of activity upon oral administration, which could be attributed to low oral absorption. The propanoyloxy isobutyl ester of the trans-4-cyclohexyl proline analog exhibited improved oral activity and long duration of action (DeForrest et al., 1989) and was advanced into preclinical and clinical development (Duchin, 1991).

Keywords

Angiotensin Convert Enzyme Angiotensin Convert Enzyme Inhibitor Phosphinic Acid Pyroglutamic Acid Active Angiotensin Convert Enzyme Inhibitor 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cushman DW, and Ondetti MA. Design of Angiotensin Converting Enzyme Inhibitors. Nat Med 1999; 5:1110–1113.PubMedCrossRefGoogle Scholar
  2. Davis R, Coukell A, and McTavish D. Fosinopril — A Review of its Pharmacology and Clinical Efficacy in the Management of Heart Failure. Drugs 1997; 54:103–116PubMedCrossRefGoogle Scholar
  3. DeForrest J, Waldron T, Harvey C, Scalese B, Rubin B, Powell J, Petrillo E, and Cushman D. Fosinopril, a Phosphinic Acid Inhibitor of Angiotensin I Converting Enzyme: In Vitro and Preclinical In Vivo Pharmacology. J Cardiovasc Pharmacol 1989; 14:730–736PubMedCrossRefGoogle Scholar
  4. Duchin K. Clinical Pharmacology of Fosinopril. Drug Invest 1991; 3(Suppl.4):12–17Google Scholar
  5. Fischler M P, and Follath F. Comparative Evaluation of ACE-inhibitors: Which Differences Are Relevant? Schweiz Med Woch 1999; 129:1053–1060Google Scholar
  6. Friedman D, and Amidon G. Passive and Carrier-Mediated Intestinal Absorption Components of Two Angiotensin Converting Enzyme (ACE) Inhibitor Prodrugs in Rats; Enalapril and Fosinopril. Pharm Res 1989; 6:1043–1047PubMedCrossRefGoogle Scholar
  7. Hilleman D. Role of Angiotensin-converting-enzyme Inhibitors in the Treatment of Hypertension. Am Soc Health Sys Pharm 2000; 57(Suppl 1)S8–S11Google Scholar
  8. Kleeman A, Engel J, Kutscher B, and Reichert D. Pharmaceutical Substances. 3rd ed. Stuttgart: Georg Thieme Verlag; 1999. 875pGoogle Scholar
  9. Krapcho J, Turk C, Cushman DW, Powell JR, DeForrest JM, Spitzmiller ER, Karanewsky DS, Duggan M, Rovnyak G, Schwartz J, Natarajan S, Godfrey, JD, Ryono DR, Neubeck R, Atwal KS, and Petrillo EW. Angiotensin-converting Enzyme Inhibitors. Mercaptan, Carboxyalkyl Dipeptide, and Phosphinic Acid Inhibitors Incorporating 4-Substituted Prolines. J Med Chem 1988; 31:1148–1160PubMedCrossRefGoogle Scholar
  10. Morrison R, Singhvi S, Peterson A, Pocetti D, and Migdalof B. Relative Contribution of the Gut, Liver, and Lung to the First-Pass Hydrolysis (Bioactivation) of Orally Administered C Fosinopril Sodium in Dogs. Drug Met Disp 1990; 18:253–257Google Scholar
  11. Ondetti MA. From Peptides to Peptidases: A Chronicle of Drug Discovery. Ann Rev Pharmacol 1994; 39:1–34Google Scholar
  12. Shu C, Shen H, Hopfer U, and Smith D. Mechanism of Intestinal Absorption and Renal Reabsorption of an orally active Ace Inhibitor: Uptake and Transport of Fosinopril in Cell Cultures. Drug Met Disp 2001; 29:1307–1315Google Scholar
  13. Thakur A, Morris K, Grosso J, Himes K, Thottahil J, Jerzewski R, Wadke D, and Carstensen T. Mechanism and Kinetics of Metal Ion-Mediated Degradation of Fosinopril Sodium. Pharm Res 1993; 10:800–809PubMedCrossRefGoogle Scholar
  14. Wang Z, Morris K, and Chu B. Aggregation Behavior of Fosinopril Sodium — A New Angiotensin-Converting Enzyme Inhibitor. J Pharm Sci 1995; 84:609–613PubMedCrossRefGoogle Scholar
  15. White C. Pharmacologic, Pharmacokinetic, and Therapeutic Differences among ACE Inhibitors. Pharmacother 1998; 18:588–599Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Edward W. Petrillo
    • 1
  1. 1.Bristol Myers Squibb Pharmaceutical Research InstitutePrincetonUSA

Personalised recommendations