Benazepril

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(New page: <applet load="" size="480" color="" frame="true" spin="on" Scene ="Enalapril/Enal/1" align="right" caption="Enalaprilat, the metabolite of Enalapril, also known as Vasotec"/> ===Better ...)
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<applet load="" size="480" color="" frame="true" spin="on" Scene ="Enalapril/Enal/1" align="right" caption="Enalaprilat, the metabolite of Enalapril, also known as Vasotec"/>
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<StructureSection load='' size='340' side='right' caption='Benazepril, also known as Lotensin' scene='Benazepril/Benazepril/1'>
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===Better Known as: Vasotec===
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===Better Known as: Lotensin (Lotrel when combined with Amlodipine)===
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* Marketed By: Merck & Co.<br />
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* Marketed By: Novartis International AG<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
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* Date of FDA Approval (Patent Expiration): 1985 (2000)<br />
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* Date of FDA Approval (Patent Expiration): 1991 (2003)<br />
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* 1996 Peak Sales: $2.5 Billion
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* 2002 Sales (Lotrel 2005 Sales): $300 Million ($1.2 Billion)
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* Why You Should Care: 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.
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* Importance: One of the earliest and best selling [[Angiotensin-Converting Enzyme]] Inhibitors of all time.
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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===
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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>
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===Mechanism of Action===
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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|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.<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>
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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

Benazepril, also known as Lotensin

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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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