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Lisinopril
From Proteopedia
(Difference between revisions)
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* 1998 Sales: $690 Million | * 1998 Sales: $690 Million | ||
* Importance: It is the only [[Angiotensin-Converting Enzyme]] Inhibitor that is not a prodrug and is excreted unchanged in the urine. Was one of the best selling ACE inhibitors in history. | * Importance: It is the only [[Angiotensin-Converting Enzyme]] Inhibitor that is not a prodrug and is excreted unchanged in the urine. Was one of the best selling ACE inhibitors in history. | ||
| - | * | + | * See [[Pharmaceutical Drugs]] for more information about other drugs and diseases. |
| + | |||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
Angiotensin II has been implicated in cardiac, renal and vascular diseases. <ref>PMID:17083068</ref> 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. | Angiotensin II has been implicated in cardiac, renal and vascular diseases. <ref>PMID:17083068</ref> 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. | ||
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{| class="wikitable" border="1" width="50%" style="text-align:center" | {| class="wikitable" border="1" width="50%" style="text-align:center" | ||
|- | |- | ||
| - | ! colspan="8" align="center"| ACE-Inhibitor [[ | + | ! colspan="8" align="center"| ACE-Inhibitor [[Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID: 7867683</ref><ref>DOI: 10.1111/j.1365-2710.2005.00646.x</ref><ref>PMID: 16075412</ref><ref>PMID:7527101</ref> |
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! Parameter | ! Parameter | ||
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! [[Trandolapril]] | ! [[Trandolapril]] | ||
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| - | ! [[ | + | ! [[Pharmacokinetics#Tmax|T<sub>max</sub>]] (hr) |
! .98 | ! .98 | ||
! 6.5 | ! 6.5 | ||
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! .72 | ! .72 | ||
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| - | ! [[ | + | ! [[Pharmacokinetics#Cmax|C<sub>max</sub>]] (ng/ml) |
! 1210 | ! 1210 | ||
! 79 | ! 79 | ||
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! 1.68 | ! 1.68 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Bioavailability_.28F.29|Bioavailability]] (%) |
! 72 | ! 72 | ||
! 25 | ! 25 | ||
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! 10 | ! 10 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Protein_Binding|Protein Binding]] (%) |
! 97 | ! 97 | ||
! 0 | ! 0 | ||
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! 80 | ! 80 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr) |
! .56 | ! .56 | ||
! 10.1 | ! 10.1 | ||
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! .68 | ! .68 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr) |
! 1673 | ! 1673 | ||
! 1016 | ! 1016 | ||
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! 1.86 | ! 1.86 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM) |
! 1.1 | ! 1.1 | ||
! 5.5 | ! 5.5 | ||
Revision as of 11:22, 9 December 2010
|
Better Known as: Prinivil
- Marketed By: Merck & Co.
- Major Indication: Hypertension & Congestive Heart Failure
- Drug Class: ACE Inhibitor
- Date of FDA Approval (Patent Expiration): 1988 (2001)
- 1998 Sales: $690 Million
- Importance: It is the only Angiotensin-Converting Enzyme Inhibitor that is not a prodrug and is excreted unchanged in the urine. Was one of the best selling ACE inhibitors in history.
- 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. Lisinopril binds to the active site of , utilizing residues like as well as van der Waals interactions between the phenylpropyl group and Val 518. [2] Binding by Lisinopril actively inhibits ACE-1 binding and conversion of angiotensin 1 into angiotensin II.
Pharmacokinetics
| ACE-Inhibitor Pharmacokinetics Comparison at Equivalent Dosages [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
- ↑ Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR. Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. PMID:15236580 doi:10.1021/bi049480n
- ↑ 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
