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Enalapril: Difference between revisions

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New page: <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 Know...
 
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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"/>
<StructureSection load='' size='340' side='right' caption='Enalaprilat, the metabolite of Enalapril, also known as Vasotec' scene='Enalapril/Enal/1'>
===Better Known as: Altace or Ramipro===
===Better Known as: Vasotec===
* Marketed By: King Pharmaceuticals (Now part of Pfizer Inc.)<br />
* Marketed By: Merck & Co.<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): 1991 (2007)<br />
* Date of FDA Approval (Patent Expiration): 1985 (2000)<br />
* 2006 Sales: $650 Million
* 1996 Peak Sales: $2.5 Billion
* Why You Should Care: One of the best selling [[Angiotensin-Converting Enzyme]] Inhibitors of all time.
* Importance: One of the best selling [[Angiotensin-Converting Enzyme]] Inhibitors of all time. Was developed by Merck as a replacement for [[Captopril]] with a better side effect profile.  
* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information
* 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. Enalapril is quickly metabolized into Enalaprilat, the more active metabolite of Enalapril predominantly by the Hepatic enzyme CYP3A4. Enalaprilat binds to the active site of <scene name='Enalapril/Ace/1'>Angiotensin-Converting Enzyme</scene>, preventing ACE-1 from binding and converting Angiotensin I into Angiotensin II. <scene name='Enalapril/Enalalprilat/2'>Enalaprilat is bound </scene>to ACE-1 via electrostatic interactions with His 353, Ala 354 (Backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520 and Tyr 523 along with the zinc cation. <ref>PMID:15236580</ref>
Ramipril is quickly metabolized into Ramiprilat, the most active inhibitor of Ramipril. Ramiprilat binds to the active site of <scene name='Ramipril/Angio/1'>Angiotensin-Converting Enzyme</scene>, actively inhibiting ACE-1 from binding and converting Angiotensin I into Angiotensin II. ACE-1 <scene name='Ramipril/Ramiprilat_binding/1'> binds Ramiprilat</scene> 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.  
</StructureSection>
 
===Pharmacokinetics===
===Pharmacokinetics===
{| class="wikitable" border="1" width="50%" style="text-align:center"
<table style="background: cellspacing="0px"  align="" cellpadding="0px" width="42%">
|-
<tr>
!  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>
<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
|-
<div style="height:100%; width: 100%">
! Parameter
{{:ACE Inhibitor Pharmacokinetics}}
! [[Captopril]]
</div>
! [[Lisinopril]]
</td>
! [[Ramipril]]
</tr>
! [[Enalapril]]
</table>
! [[Benazepril]]
! [[Perindopril]]
! [[Trandolapril]]
|-
! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)
! .98
! 6.5
! .67
! 1.06
! .5
! .75
! .72
|-
! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml)
! 1210
! 79
! 16.4
! 314
! 149
! 105
! 1.68
|-
! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
! 72
! 25
! 28
! 60
! 97
! 24
! 10
|-
! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
! 97
! 0
! 73
! 20
! 97
! 20
! 80
|-
! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
! .56
! 10.1
! 1.93
! 1.6
! 10
! .9
! .68
|-
! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
! 1673
! 1016
! 21.9
! 450
! 140
! 182
! 1.86
|-
! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (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==
==References==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky
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