Ramipril

Better Known as: Altace or Ramipro

Marketed By: King Pharmaceuticals (Now part of Pfizer Inc.)
Major Indication: Hypertension & Congestive Heart Failure
Drug Class: ACE Inhibitor
Date of FDA Approval (Patent Expiration): 1991 (2007)
2006 Sales: $650 Million
Importance: One of the best selling Angiotensin-Converting Enzyme Inhibitors of all time. Long acting ACE Inhibitor.
See Pharmaceutical Drugs for more information about other drugs and diseases

Mechanism of Action

Angiotensin II has been implicated in cardiac, renal and vascular diseases. ^[1] Bradykinin, a small peptide that counterbalance the effects of Angiotensin II by acting as a strong vasodilator upon binding AT2, is degraded by the same ACE-1 enzyme. Since ACE-1 is the primary producer of Angiotensin II and degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Ramipril is quickly metabolized into Ramiprilat, the most active metabolite of Ramipril. Ramiprilat binds to the active site of , actively inhibiting ACE-1 from binding and converting Angiotensin I into Angiotensin II. ACE-1 using residues Glu 395, His 497, Lys 495, Gln 265, Tyr 504, Tyr 496 and Tyr 507, tightly affixing the inhibitor to the active site of ACE-1.

Pharmacokinetics

ACE-Inhibitor Pharmacokinetics Comparison at Equivalent Dosages ^[2]^[3]^[4]^[5]
Parameter	Captopril	Lisinopril	Ramipril	Enalapril	Benazepril	Perindopril	Trandolapril
T_max (hr)	.98	6.5	.67	1.06	.5	.75	.72
C_max (ng/ml)	1210	79	16.4	314	149	105	1.68
Bioavailability (%)	72	25	28	60	97	24	10
Protein Binding (%)	97	0	73	20	97	20	80
T_1/2 (hr)	.56	10.1	1.93	1.6	10	.9	.68
AUC (ng/ml/hr)	1673	1016	21.9	450	140	182	1.86
IC₅₀ (nM)	1.1	5.5	5.0	5.4	1.7	2.4	2.5
Dosage (mg)	10	20	5	20	10	4	2
Metabolism	Hepatic (CYP2D6)	None	Hepatic	Hepatic (CYP3A4)	Hepatic	Hepatic	Hepatic (CYP2D6 & CYP2C9)

References

↑ Ferrario CM. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J Renin Angiotensin Aldosterone Syst. 2006 Mar;7(1):3-14. PMID:17083068
↑ Sun JX, Cipriano A, Chan K, John VA. Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects. Eur J Clin Pharmacol. 1994;47(3):285-9. PMID:7867683
↑ Arafat T, Awad R, Hamad M, Azzam R, Al-Nasan A, Jehanli A, Matalka K. Pharmacokinetics and pharmacodynamics profiles of enalapril maleate in healthy volunteers following determination of enalapril and enalaprilat by two specific enzyme immunoassays. J Clin Pharm Ther. 2005 Aug;30(4):319-28. PMID:15985045 doi:10.1111/j.1365-2710.2005.00646.x
↑ Tamimi JJ, Salem II, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of lisinopril tablets (Lisotec and Zestril) in healthy human volunteers. Biopharm Drug Dispos. 2005 Nov;26(8):335-9. PMID:16075412 doi:10.1002/bdd.465
↑ Arner P, Wade A, Engfeldt P, Mouren M, Stepniewski JP, Sultan E, Bryce T, Lenfant B. Pharmacokinetics and pharmacodynamics of trandolapril after repeated administration of 2 mg to young and elderly patients with mild-to-moderate hypertension. J Cardiovasc Pharmacol. 1994;23 Suppl 4:S44-9. PMID:7527101

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky

[1] Ferrario CM. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J Renin Angiotensin Aldosterone Syst. 2006 Mar;7(1):3-14. PMID:17083068

[2] Sun JX, Cipriano A, Chan K, John VA. Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects. Eur J Clin Pharmacol. 1994;47(3):285-9. PMID:7867683

[3] Arafat T, Awad R, Hamad M, Azzam R, Al-Nasan A, Jehanli A, Matalka K. Pharmacokinetics and pharmacodynamics profiles of enalapril maleate in healthy volunteers following determination of enalapril and enalaprilat by two specific enzyme immunoassays. J Clin Pharm Ther. 2005 Aug;30(4):319-28. PMID:15985045 doi:10.1111/j.1365-2710.2005.00646.x

[4] Tamimi JJ, Salem II, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of lisinopril tablets (Lisotec and Zestril) in healthy human volunteers. Biopharm Drug Dispos. 2005 Nov;26(8):335-9. PMID:16075412 doi:10.1002/bdd.465

[5] Arner P, Wade A, Engfeldt P, Mouren M, Stepniewski JP, Sultan E, Bryce T, Lenfant B. Pharmacokinetics and pharmacodynamics of trandolapril after repeated administration of 2 mg to young and elderly patients with mild-to-moderate hypertension. J Cardiovasc Pharmacol. 1994;23 Suppl 4:S44-9. PMID:7527101

[1]

[2]

[3]

[4]

[5]