Captopril
From Proteopedia
(Difference between revisions)
| Line 2: | Line 2: | ||
===Better Known as: Capoten=== | ===Better Known as: Capoten=== | ||
* Marketed By: Bristol-Myers Squibb<br /> | * Marketed By: Bristol-Myers Squibb<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): 1981 (1996)<br /> | * Date of FDA Approval (Patent Expiration): 1981 (1996)<br /> | ||
Revision as of 11:40, 29 November 2010
|
Better Known as: Capoten
- Marketed By: Bristol-Myers Squibb
- Major Indication: Hypertension & Congestive Heart Failure
- Drug Class: ACE Inhibitor
- Date of FDA Approval (Patent Expiration): 1981 (1996)
- 2009 Sales: N/A
- Why You Should Care: It was the first Angiotensin-Converting Enzyme Inhibitor. Was one of the earliest successes of Structure-Based drug design paving the way for future discoveries.
- The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information
Mechanism of Action
Extensive research has validated a pathological role for Angiotensin II 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 primary degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Captopril binds to the ACE-1 binding site of , preventing ACE-1 from binding angiotensin. Captopril,, forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation. [2]
Pharmacokinetics
| ACE-Inhibitor Pharmacokinetics Comparison at Equivalent Dosages [3][4][5][6][7] | |||||||
|---|---|---|---|---|---|---|---|
| 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
- ↑ 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
