Perindopril: Difference between revisions

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* 2005 Sales: $1 Billion
* 2005 Sales: $1 Billion
* Importance: 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.
* 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.  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]].<ref>PMID:17083068</ref> Perindopril is rapidly metabolized into its highly active metabolite Perindoprilat by hepatic enzymes. Perindoprilat binds to the active site of <scene name='Perindopril/Perindoprilat_ace/1'>Angiotensin-Converting Enzyme</scene>, actively inhibiting ACE-1 from binding and converting Angiotensin I into Angiotensin II. ACE-1 <scene name='Perindopril/Perindoprilat_binding/1'>binds Perindoprilat</scene> using residues Gln 265, Lys 495, Tyr 504, His 497, His 337, Tyr 496, Ala 338, Glu 368, His 367, HIs 371, Glu 395 and Asp 399 to tightly affix the inhibitor to the active site of ACE-1.  
Angiotensin II has been implicated in cardiac, renal and vascular diseases.  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]].<ref>PMID:17083068</ref> Perindopril is rapidly metabolized into its highly active metabolite Perindoprilat by hepatic enzymes. Perindoprilat binds to the active site of <scene name='Perindopril/Perindoprilat_ace/1'>Angiotensin-Converting Enzyme</scene>, actively inhibiting ACE-1 from binding and converting Angiotensin I into Angiotensin II. ACE-1 <scene name='Perindopril/Perindoprilat_binding/1'>binds Perindoprilat</scene> using residues Gln 265, Lys 495, Tyr 504, His 497, His 337, Tyr 496, Ala 338, Glu 368, His 367, HIs 371, Glu 395 and Asp 399 to tightly affix the inhibitor to the active site of ACE-1.  
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{| class="wikitable" border="1" width="50%" style="text-align:center"
{| 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: 16075412</ref><ref>PMID:7527101</ref>
!  colspan="8" align="center"| ACE-Inhibitor [[Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID: 7867683</ref><ref>DOI: 10.1111/j.1365-2710.2005.00646.x</ref><ref>PMID: 16075412</ref><ref>PMID:7527101</ref>
|-
|-
! Parameter
! Parameter
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! [[Trandolapril]]
! [[Trandolapril]]
|-
|-
! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)  
! [[Pharmacokinetics#Tmax|T<sub>max</sub>]] (hr)  
! .98
! .98
! 6.5
! 6.5
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! .72
! .72
|-
|-
! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml)  
! [[Pharmacokinetics#Cmax|C<sub>max</sub>]] (ng/ml)  
! 1210
! 1210
! 79
! 79
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! 1.68
! 1.68
|-
|-
! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
! [[Pharmacokinetics#Bioavailability_.28F.29|Bioavailability]] (%)
! 72
! 72
! 25
! 25
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! 10
! 10
|-
|-
! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
! [[Pharmacokinetics#Protein_Binding|Protein Binding]] (%)
! 97
! 97
! 0
! 0
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! 80
! 80
|-
|-
! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
! [[Pharmacokinetics#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
! .56
! .56
! 10.1
! 10.1
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! .68
! .68
|-
|-
! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
! 1673
! 1673
! 1016
! 1016
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! 1.86
! 1.86
|-
|-
! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM)
! [[Pharmacokinetics#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM)
! 1.1
! 1.1
! 5.5
! 5.5
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