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Ramipril

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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"/>
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<StructureSection load='' size='340' side='right' caption='Ramiprilat, the metabolite of Ramipril, also known as Altace' scene='Ramipril/Rama/1'>
===Better Known as: Altace or Ramipro===
===Better Known as: Altace or Ramipro===
* Marketed By: King Pharmaceuticals (Now part of Pfizer Inc.)<br />
* Marketed By: King Pharmaceuticals (Now part of Pfizer Inc.)<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): 1991 (2007)<br />
* Date of FDA Approval (Patent Expiration): 1991 (2007)<br />
* 2006 Sales: $650 Million
* 2006 Sales: $650 Million
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* Why You Should Care: One of the best selling [[Angiotensin-Converting Enzyme]] Inhibitors of all time.
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* Importance: One of the best selling [[Angiotensin-Converting Enzyme]] Inhibitors of all time. Long acting ACE Inhibitor.
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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===
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.
Ramipril is quickly metabolized into Ramiprilat, the most active metabolite 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.
Ramipril is quickly metabolized into Ramiprilat, the most active metabolite 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.
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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>
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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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! 79
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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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! 1016
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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

Ramiprilat, the metabolite of Ramipril, also known as Altace

Drag the structure with the mouse to rotate

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


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David Canner, Alexander Berchansky

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