Perindopril: Difference between revisions
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<applet load="" size="480" color="" frame="true" spin="on" Scene ="Ramipril/Rama/1" align="right" caption="Ramiprilat, the metabolite of Ramipril, also known as Altace"/> | <applet load="" size="480" color="" frame="true" spin="on" Scene ="Ramipril/Rama/1" align="right" caption="Ramiprilat, the metabolite of Ramipril, also known as Altace"/> | ||
===Better Known as: | ===Better Known as: Aceon=== | ||
* Marketed By: | * Marketed By: Abbot Labs<br /> | ||
* Major Indication: Hypertension & Congestive Heart Failure<br /> | * Major Indication: [[Hypertension & Congestive Heart Failure]]<br /> | ||
* Drug Class: [[ACE]] Inhibitor | * Drug Class: [[ACE]] Inhibitor | ||
* Date of FDA Approval (Patent Expiration): | * Date of FDA Approval (Patent Expiration): 1993 (2009)<br /> | ||
* 2006 Sales: $650 Million | * 2006 Sales: $650 Million | ||
* Why You Should Care: One of the best selling [[Angiotensin-Converting Enzyme]] Inhibitors of all time. | * Why You Should Care: One of the best selling [[Angiotensin-Converting Enzyme]] Inhibitors of all time. | ||
Revision as of 12:02, 29 November 2010
|
Better Known as: Aceon
- Marketed By: Abbot Labs
- Major Indication: Hypertension & Congestive Heart Failure
- Drug Class: ACE Inhibitor
- Date of FDA Approval (Patent Expiration): 1993 (2009)
- 2006 Sales: $650 Million
- Why You Should Care: One of the best selling Angiotensin-Converting Enzyme Inhibitors of all time.
- The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information
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 Angiotensin-Converting Enzyme, actively inhibiting ACE-1 from binding and converting Angiotensin I into Angiotensin II. ACE-1 binds Ramiprilat 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][6] | |||||||
|---|---|---|---|---|---|---|---|
| Parameter | Captopril | Lisinopril | Ramipril | Enalapril | Benazepril | Perindopril | Trandolapril |
| Tmax (hr) | .98 | 6.5 | .67 | 1.06 | .5 | .75 | .72 |
| Cmax (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 |
| T1/2 (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
- ↑ 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
