Captopril

Better Known as: Capoten Marketed By: Bristol-Myers Squibb Major Indication: Hypertension & Congestive Heart Failure Drug Class: ACE Inhibitor Date of FDA Approval (Patent Expiration): 1981 (1996) 2009 Sales: N/A Importance: It was the first Angiotensin-Converting Enzyme Inhibitor. Was one of the earliest successes of Structure-Based drug design paving the way for future discoveries. See Pharmaceutical Drugs for more information about other drugs and diseases Mechanism of Action Extensive research has validated a pathological role for Angiotensin II 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 primary degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Captopril binds to the ACE-1 binding site of , preventing ACE-1 from binding angiotensin. Captopril,, forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation.

spinqualitylabelsall models Captopril, also known as Capoten Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Pharmacokinetics

ACE-Inhibitor Pharmacokinetics Comparison at Equivalent Dosages Parameter Captopril Lisinopril Ramipril Enalapril 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