Lisinopril

spinqualitylabelsall models Lisinopril, also known as Prinivil Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Prinivil Marketed By: Merck & Co. Major Indication: Hypertension & Congestive Heart Failure Drug Class: ACE Inhibitor Date of FDA Approval (Patent Expiration): 1988 (2001) 1998 Sales: $690 Million 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. 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 and Congestive Heart Failure. Lisinopril binds to the active site of Angiotensin-Converting Enzyme, utilizing residues like His 353, Ala 354 (backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520, Tyr 523 and Glu 162 as well as van der Waals interactions between the phenylpropyl group and Val 518. Binding by Lisinopril actively inhibits ACE-1 binding and conversion of angiotensin 1 into angiotensin II.

Pharmacokinetics

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