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Clinical data
Trade namesMonopril
  • AU: D
Routes of
By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding87% (fosinoprilat)
Metabolismliver, GIT mucosa (to fosinoprilat)
Elimination half-life12 hours (fosinoprilat)
  • (2S,4S)-4-cyclohexyl-1-[2-[hydroxy(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
Molar mass563.672 g·mol−1
3D model (JSmol)
  • O=C(CP(=O)(CCCCc1ccccc1)OC(OC(=O)CC)C(C)C)N2C[C@@H](C[C@H]2C(O)=O)C3CCCCC3
  • InChI=1S/C30H46NO7P/c1-4-28(33)37-30(22(2)3)38-39(36,18-12-11-15-23-13-7-5-8-14-23)21-27(32)31-20-25(19-26(31)29(34)35)24-16-9-6-10-17-24/h5,7-8,13-14,22,24-26,30H,4,6,9-12,15-21H2,1-3H3,(H,34,35)/t25-,26+,30?,39-/m1/s1 checkY
 ☒NcheckY (what is this?)  (verify)

Fosinopril is an angiotensin converting enzyme (ACE) inhibitor[1] used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphonate-containing ACE inhibitor marketed, by Bristol-Myers Squibb under the trade name Monopril. Fosinopril is a cascading pro-drug. The special niche for the medication that differentiates it from the other members of the ACE Inhibitor drug class is that was specifically developed for the use for patients with renal impairment. This was through manipulation of the metabolism and excretion, and is seen that fifty percent of the drug is hepatobiliary cleared, which can compensate for diminished renal clearance. The remaining fifty percent is excreted in urine. It does not need dose adjustment.

It was patented in 1980 and approved for medical use in 1991.[2]

Medical uses[edit]

In congestive heart failure, the ability of the heart to pump enough blood to satisfy the physiological needs of the body is reduced.[3] This condition has a variety of causes, including damaged heart valves, myocardial infarction, hypertension, vitamin B1 deficiency, and genetic mutations. When subsequent blood flow to the kidneys is reduced, the kidneys respond by increasing the secretion of renin from the juxtaglomerular apparatus. Renin converts the inactive angiotensinogen into angiotensin I, which is converted to angiotensin II (AII) by angiotensin converting enzyme (ACE). AII can have negative effects on the cardiovascular system after events such as heart failure and myocardial infarction. AII causes arterial vasoconstriction and hypertension, resulting in an increase in afterload, increasing the resistance against which the heart works.[4] Additionally, chronic increase in production of AII is associated with structural changes to the myocardium[5] which reduces the functionality of the heart.[4]

In heart failure patients, fosinopril increases exercise tolerance and lowers the frequency of events associated with worsening heart failure, such as dyspnea, the need for supplemental diuretics, fatigue, and hospitalizations.[6]


Unlike other ACE inhibitors that are primarily excreted by the kidneys, fosinopril is eliminated from the body by both renal and hepatic pathways.[7] This characteristic of fosinopril makes the drug a safer choice than other ACE inhibitors for heart failure patients with impaired kidney function resulting from poor perfusion[8] as fosinopril can still be eliminated by the liver, preventing accumulation of the drug in the body.[7]

Fosinopril is de-esterified by the liver or gastrointestinal mucosa and is converted to its active form, fosinoprilat.[9] Fosinoprilat competitively binds to ACE, preventing ACE from binding to and converting angiotensin I to angiotensin II. Inhibiting the production of AII lowers peripheral vascular resistance, decreases afterload, and decreases blood pressure,[4] thus helping to alleviate the negative effects of AII on cardiac performance.


  1. ^ Pilote L, Abrahamowicz M, Eisenberg M, Humphries K, Behlouli H, Tu JV (May 2008). "Effect of different angiotensin-converting-enzyme inhibitors on mortality among elderly patients with congestive heart failure". CMAJ. 178 (10): 1303–1311. doi:10.1503/cmaj.060068. PMC 2335176. PMID 18458262.
  2. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 468. ISBN 9783527607495.
  3. ^ Guyton AC, Hall JE (2006). Textbook of medical physiology: online access + interactive extras: (11th ed.). Philadelphia, Pa: Elsevier, Saunders. ISBN 978-0-7216-0240-0.
  4. ^ a b c Katzung BG, Masters SB, Trevor AJ (2009). Basic and Clinical Pharmacology (11th ed.). New York: McGraw-Hill. ISBN 978-0-07-160405-5.
  5. ^ Yamagishi H, Kim S, Nishikimi T, Takeuchi K, Takeda T (November 1993). "Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats". Journal of Molecular and Cellular Cardiology. 25 (11): 1369–1380. doi:10.1006/jmcc.1993.1149. PMID 8301670.
  6. ^ Erhardt L, MacLean A, Ilgenfritz J, Gelperin K, Blumenthal M (December 1995). "Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group". European Heart Journal. 16 (12): 1892–1899. doi:10.1093/oxfordjournals.eurheartj.a060844. PMID 8682023.
  7. ^ a b Zannad F, Chati Z, Guest M, Plat F (October 1998). "Differential effects of fosinopril and enalapril in patients with mild to moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators". American Heart Journal. 136 (4 Pt 1): 672–680. doi:10.1016/s0002-8703(98)70015-8. PMID 9778071.
  8. ^ Greenbaum R, Zucchelli P, Caspi A, Nouriel H, Paz R, Sclarovsky S, et al. (January 2000). "Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency". British Journal of Clinical Pharmacology. 49 (1): 23–31. doi:10.1046/j.1365-2125.2000.00103.x. PMC 2014892. PMID 10606834.
  9. ^ Duchin KL, Waclawski AP, Tu JI, Manning J, Frantz M, Willard DA (January 1991). "Pharmacokinetics, safety, and pharmacologic effects of fosinopril sodium, an angiotensin-converting enzyme inhibitor in healthy subjects". Journal of Clinical Pharmacology. 31 (1): 58–64. doi:10.1002/j.1552-4604.1991.tb01887.x. PMID 1646240. S2CID 24683211.