Captopril

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	===Pharmacokinetics===		===Pharmacokinetics===
-	{| class="wikitable" border="1" width="50%" style="text-align:center"	+	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">
-	|-	+	<tr>
-	! colspan="8" align="center"| ACE-Inhibitor [[Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID: 7867683</ref><ref>DOI: 10.1111/j.1365-2710.2005.00646.x</ref><ref>PMID: 16075412</ref><ref>PMID:7527101</ref>	+	<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
-	|-	+	<div style="height:100%; width: 100%">
-	! Parameter	+	{{:ACE Inhibitor Pharmacokinetics}}
-	! [[Captopril]]	+	</div>
-	! [[Lisinopril]]	+	</td>
-	! [[Ramipril]]	+	</tr>
-	! [[Enalapril]]	+	</table>
-	! [[Benazepril]]	+
-	! [[Perindopril]]	+
-	! [[Trandolapril]]	+
-	|-	+
-	! [[Pharmacokinetics#Tmax|T<sub>max</sub>]] (hr)	+
-	! .98	+
-	! 6.5	+
-	! .67	+
-	! 1.06	+
-	! .5	+
-	! .75	+
-	! .72	+
-	|-	+
-	! [[Pharmacokinetics#Cmax|C<sub>max</sub>]] (ng/ml)	+
-	! 1210	+
-	! 79	+
-	! 16.4	+
-	! 314	+
-	! 149	+
-	! 105	+
-	! 1.68	+
-	|-	+
-	! [[Pharmacokinetics#Bioavailability_.28F.29|Bioavailability]] (%)	+
-	! 72	+
-	! 25	+
-	! 28	+
-	! 60	+
-	! 97	+
-	! 24	+
-	! 10	+
-	|-	+
-	! [[Pharmacokinetics#Protein_Binding|Protein Binding]] (%)	+
-	! 97	+
-	! 0	+
-	! 73	+
-	! 20	+
-	! 97	+
-	! 20	+
-	! 80	+
-	|-	+
-	! [[Pharmacokinetics#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)	+
-	! .56	+
-	! 10.1	+
-	! 1.93	+
-	! 1.6	+
-	! 10	+
-	! .9	+
-	! .68	+
-	|-	+
-	! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)	+
-	! 1673	+
-	! 1016	+
-	! 21.9	+
-	! 450	+
-	! 140	+
-	! 182	+
-	! 1.86	+
-	|-	+
-	! [[Pharmacokinetics#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (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)	+
-	|}	+
	==References==		==References==

---

Revision as of 09:14, 10 December 2010

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. ^[1] 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. ^[2]

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

References

1. ↑ Ferrario CM. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J Renin Angiotensin Aldosterone Syst. 2006 Mar;7(1):3-14. PMID:17083068
2. ↑ Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR. Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. PMID:15236580 doi:10.1021/bi049480n