Captopril
From Proteopedia
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| - | ! colspan="8" align="center"| ACE-Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated|Pharmacokinetics]] Comparison at Equivalent Dosages | + | ! colspan="8" align="center"| ACE-Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated|Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID: 7867683</ref> <ref>DOI: 10.1111/j.1365-2710.2005.00646.x</ref> <ref>PMID: 15985045</ref> |
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! Parameter | ! Parameter | ||
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! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr) | ! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr) | ||
| - | ! | + | ! .98 |
| - | ! | + | ! 6.5 |
| - | ! | + | ! .67 |
| - | ! | + | ! 1.06 |
! | ! | ||
! | ! | ||
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! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml) | ! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml) | ||
| - | ! | + | ! 1210 |
| - | ! | + | ! 79800 |
| - | ! | + | ! 16.4 |
| - | ! | + | ! 314 |
! | ! | ||
! | ! | ||
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! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%) | ! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%) | ||
| - | ! | + | ! 72 |
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! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr) | ! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr) | ||
| - | ! | + | ! .56 |
| - | ! | + | ! 10.1 |
| - | ! | + | ! 1.93 |
| - | ! | + | ! 1.6 |
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! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr) | ! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr) | ||
| - | ! | + | ! 1673 |
| - | ! | + | ! 1016000 |
| - | ! | + | ! 21.9 |
| - | ! | + | ! 450 |
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! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM) | ! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM) | ||
| - | ! | + | ! 1.1 |
| - | ! | + | ! 5.5 |
| - | ! | + | ! [[Ramipril]] |
| - | ! | + | ! 5.4 |
| - | ! | + | ! [[Benazepril]] |
| - | ! | + | ! [[Perindopril]] |
| - | ! | + | ! [[Trandolapril]] |
|- | |- | ||
! Equivalent Dosage (mg) | ! Equivalent Dosage (mg) | ||
| - | ! | + | ! 10 |
| - | ! | + | ! 20 |
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! | ! | ||
Revision as of 18:21, 28 November 2010
|
Contents |
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.
- 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] | |||||||
|---|---|---|---|---|---|---|---|
| Parameter | Captopril | Lisinopril | Ramipril | Enalapril | Benazepril | Perindopril | Trandolapril |
| Tmax (hr) | .98 | 6.5 | .67 | 1.06 | |||
| Cmax (ng/ml) | 1210 | 79800 | 16.4 | 314 | |||
| Bioavailability (%) | 72 | ||||||
| Protein Binding (%) | 96.7 | ||||||
| T1/2 (hr) | .56 | 10.1 | 1.93 | 1.6 | |||
| AUC (ng/ml/hr) | 1673 | 1016000 | 21.9 | 450 | |||
| IC50 (nM) | 1.1 | 5.5 | Ramipril | 5.4 | Benazepril | Perindopril | Trandolapril |
| Equivalent Dosage (mg) | 10 | 20 | |||||
| Metabolism | |||||||
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
