Ramipril

spinqualitylabelsall models Ramiprilat, the metabolite of Ramipril, also known as Altace Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Altace or Ramipro Marketed By: King Pharmaceuticals (Now part of Pfizer Inc.) Major Indication: Hypertension & Congestive Heart Failure Drug Class: ACE Inhibitor Date of FDA Approval (Patent Expiration): 1991 (2007) 2006 Sales: $650 Million Importance: One of the best selling Angiotensin-Converting Enzyme Inhibitors of all time. Long acting ACE Inhibitor. 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. Ramipril is quickly metabolized into Ramiprilat, the most active metabolite of Ramipril. Ramiprilat 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 Ramiprilat using residues Glu 395, His 497, Lys 495, Gln 265, Tyr 504, Tyr 496 and Tyr 507, tightly affixing 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 Ramipril 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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