Trandolapril

spinqualitylabelsall models Trandolaprilat, the metabolite of Trandolapril, also known as Mavik Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Mavik Marketed By: Abbott Labs Major Indication: Hypertension & Congestive Heart Failure Drug Class: ACE Inhibitor Date of FDA Approval (Patent Expiration): 1996 (2006) 2006 Sales: $50 Million Importance: Appears to have been an unsuccessful launch of a new Angiotensin-Converting Enzyme Inhibitor in a market with several established compounds already available. 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. Trandolapril is rapidly metabolized into its highly active metabolite Trandolaprilat by hepatic enzymes. Trandolaprilat binds to the active site of Angiotensin-Converting Enzyme, preventing ACE-1 from binding and converting Angiotensin I into Angiotensin II. ACE-1 binds Trandolaprilat using residues Tyr 496, Glu 368, Glu 395, Ser 339, Ala 338, His 367, His 371, Val 502, His 497, Lys 495, Tyr 504, Gln 265, Asp 399, Phe 441, Phe 511 and a Zinc Ion 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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