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Captopril

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<applet load="" size="480" color="" frame="true" spin="on" Scene ="Captopril/Captopril/2" align="right" caption="Captopril, also known as Capoten"/>
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<StructureSection load='' size='340' side='right' caption='Captopril, also known as Capoten' scene='Captopril/Captopril/2'>
===Better Known as: Capoten===
===Better Known as: Capoten===
* Marketed By: Bristol-Myers Squibb<br />
* Marketed By: Bristol-Myers Squibb<br />
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* Major Indication: Hypertension & Congestive Heart Failure<br />
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* 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 />
* 2009 Sales: N/A
* 2009 Sales: N/A
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* Why You Should Care: It was the first [[Angiotensin-Converting Enzyme]] Inhibitor. Was one of the earliest successes of Structure-Based drug design.
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* Importance: 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.
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* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information
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* See [[Pharmaceutical Drugs]] for more information about other drugs and diseases
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===Mechanism of Action===
===Mechanism of Action===
Extensive research has validated a pathological role for Angiotensin II 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 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 <scene name='Captopril/Ace/1'>Angiotensin-Converting enzyme</scene>, preventing ACE-1 from binding angiotensin. Captopril,<scene name='Captopril/Captopril_binding/1'> binds ACE-1 precisely</scene>, forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation. <ref>PMID:15236580</ref>
Extensive research has validated a pathological role for Angiotensin II 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 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 <scene name='Captopril/Ace/1'>Angiotensin-Converting enzyme</scene>, preventing ACE-1 from binding angiotensin. Captopril,<scene name='Captopril/Captopril_binding/1'> binds ACE-1 precisely</scene>, forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation. <ref>PMID:15236580</ref>
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</StructureSection>
===Pharmacokinetics===
===Pharmacokinetics===
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{| class="wikitable" border="1" width="50%" style="text-align:center"
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<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">
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|-
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<tr>
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! 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><ref>PMID: 16075412</ref><ref>PMID:7527101</ref><ref>ISBN:0471752158</ref>
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<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
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|-
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<div style="height:100%; width: 100%">
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! Parameter
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{{:ACE Inhibitor Pharmacokinetics}}
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! [[Captopril]]
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</div>
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! [[Lisinopril]]
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</td>
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! [[Ramipril]]
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</tr>
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! [[Enalapril]]
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</table>
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! [[Benazepril]]
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! [[Perindopril]]
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! [[Trandolapril]]
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|-
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! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)
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! .98
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! 6.5
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! .67
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! 1.06
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! .5
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! .75
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! .72
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|-
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! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml)
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! 1210
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! 79800
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! 16.4
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! 314
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! 149
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! 105
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! 1.68
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|-
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! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
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! 72
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! 25
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! 28
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! 60
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! 97
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! 24
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! 10
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|-
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! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
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! 97
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! 0
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! 73
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! 20
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! 97
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! 20
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! 80
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|-
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! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
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! .56
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! 10.1
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! 1.93
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! 1.6
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! 10
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! .9
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! .68
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|-
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! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
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! 1673
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! 1016000
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! 21.9
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! 450
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! 140
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! 182
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! 1.86
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|-
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! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM)
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! 1.1
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! 5.5
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! 5.0
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! 5.4
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! 1.7
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! 2.4
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! 2.5
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|-
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! Dosage (mg)
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! 10
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! 20
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! 5
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! 20
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! 10
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! 4
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! 2
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|-
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! Metabolism
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! Hepatic (CYP2D6)
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! None
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! Hepatic
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! Hepatic (CYP3A4)
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! Hepatic
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! Hepatic
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! Hepatic (CYP2D6 & CYP2C9)
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|}
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==References==
==References==

Current revision

Captopril, also known as Capoten

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Pharmacokinetics

ACE-Inhibitor Pharmacokinetics Comparison at Equivalent Dosages
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)

For Pharmacokinetic Data References, See: References

References

  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. ↑ 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


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David Canner, Alexander Berchansky

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