Lisinopril: Difference between revisions

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<applet  load="" size="480" color="" frame="true"  spin="on" Scene ="Lisinopril/Lisinopril/1" align="right" caption="Lisinopril, also known as Prinivil"/>
<StructureSection load='' size='340' side='right' caption='Lisinopril, also known as Prinivil' scene='Lisinopril/Lisinopril/1'>
===Better Known as: Prinivil===
===Better Known as: Prinivil===
* Marketed By: Merck & Co.<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): 1988 (2001)<br />
* Date of FDA Approval (Patent Expiration): 1988 (2001)<br />
* 1998 Sales: $690 Million
* 1998 Sales: $690 Million
* Why You Should Care: It is the only [[Angiotensin-Converting Enzyme]] Inhibitor that is not a prodrug and is excreted unchanged in the urine. Was one of the best selling ACE inhibitors in history.  
* Importance: It is the only [[Angiotensin-Converting Enzyme]] Inhibitor that is not a prodrug and is excreted unchanged in the urine. Was one of the best selling ACE inhibitors in history.  
* 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.  
Lisinopril binds to the active site of <scene name='Lisinopril/Ace/1'>Angiotensin-Converting Enzyme</scene>, utilizing residues like <scene name='Angiotensin-Converting_Enzyme/Lisinopril/1'>His 353, Ala 354 (backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520, Tyr 523 and Glu 162</scene> as well as van der Waals interactions between the phenylpropyl group and Val 518.  
Lisinopril binds to the active site of <scene name='Lisinopril/Ace/1'>Angiotensin-Converting Enzyme</scene>, utilizing residues like <scene name='Lisinopril/Lisinopril_bound/1'>His 353, Ala 354 (backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520, Tyr 523 and Glu 162</scene> as well as van der Waals interactions between the phenylpropyl group and Val 518. <ref>PMID:15236580</ref> Binding by Lisinopril actively inhibits ACE-1 binding and conversion of angiotensin 1 into angiotensin II.
&&&&l binds to the ACE-1 binding site of <scene name='Captopril/Ace/1'>Angiotensin-Converting enzyme</scene>, preventing ACE-1 from binding angiotensin. &&&&,<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>
</StructureSection>
===Pharmacokinetics===
<table style="background: cellspacing="0px"  align="" cellpadding="0px" width="42%">
<tr>
<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
<div style="height:100%; width: 100%">
{{:ACE Inhibitor Pharmacokinetics}}
</div>
</td>
</tr>
</table>


===Pharmacokinetics===
{| class="wikitable" border="1" width="50%" style="text-align:center"
|-
!  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>
|-
! Parameter
! [[Captopril]]
! [[Lisinopril]]
! [[Ramipril]]
! [[Enalapril]]
! [[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==

Latest revision as of 15:59, 10 January 2024

Better Known as: Prinivil

Mechanism of Action

Angiotensin II has been implicated 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 degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure.

Lisinopril binds to the active site of , utilizing residues like as well as van der Waals interactions between the phenylpropyl group and Val 518. [2] Binding by Lisinopril actively inhibits ACE-1 binding and conversion of angiotensin 1 into angiotensin II.

Lisinopril, also known as Prinivil

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
  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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