Perindopril

spinqualitylabelsall models Perindoprilat, the metabolite of Perindopril, also known as Aceon Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Aceon Marketed By: Abbott Labs & Servier Major Indication: Hypertension & Congestive Heart Failure Drug Class: ACE Inhibitor Date of FDA Approval (Patent Expiration): 1993 (2009) 2005 Sales: $1 Billion Importance: One of the best selling Angiotensin-Converting Enzyme Inhibitors of all time. See Pharmaceutical Drugs for more information about other drugs and diseases. 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. Perindopril is rapidly metabolized into its highly active metabolite Perindoprilat by hepatic enzymes. Perindoprilat binds to the active site of Angiotensin-Converting Enzyme, actively inhibiting ACE-1 from binding and converting Angiotensin I into Angiotensin II. ACE-1 binds Perindoprilat 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.

Pharmacokinetics

ACE-Inhibitor Hypertension & Congestive Heart Failure Comparison at Equivalent Dosages Parameter ACE Angiotensin-Converting Enzyme Pharmaceutical Drugs Hypertension 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

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