Captopril

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

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.

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