Cerivastatin: Difference between revisions

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<applet  load="" size="480" color="" frame="true"  spin="on" Scene ="Cerivastatin/Ceriv/1" align="right" caption="Cerivastatin, also known as Baycol"/>
<StructureSection load='' size='340' side='right' caption='Cerivastatin, also known as Baycol' scene='Cerivastatin/Ceriv/1'>
===Better Known as: Baycol===
===Better Known as: Baycol===
* Marketed By: Bayer <br />
* Marketed By: Bayer Healthcare<br />
* Major Indication: Hyperlipidemia & High Cholesterol ([[Metabolic Disorders|Hypercholesterolemia]])<br />
* Major Indication: Hyperlipidemia & High Cholesterol ([[Metabolic Disorders|Hypercholesterolemia]])<br />
* Drug Class: [[HMGR]] Inhibitor or Statin
* Drug Class: [[HMGR]] Inhibitor or Statin
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===Mechanism of Action===
===Mechanism of Action===
Cerivastatin is an inhibitor of [[HMG-CoA Reductase]] (HMGR), a highly <scene name='Cerivastatin/Chmg/1'>regulated enzyme</scene> responsible for the committed step in cholesterol synthesis.<ref>PMID:7784310</ref> Cerivastatin, like most of the statins, <scene name='Cerivastatin/Statin_ceriv/2'>binds HMGR</scene> via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Fluvastatin contribute to binding as well.<ref>PMID:11349148</ref> These interactions help Cerivastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.<ref>PMID:7784310</ref>
Cerivastatin is an inhibitor of [[HMG-CoA Reductase]] (HMGR), a highly <scene name='Cerivastatin/Chmg/1'>regulated enzyme</scene> responsible for the committed step in cholesterol synthesis.<ref>PMID:7784310</ref> Cerivastatin, like most of the statins, <scene name='Cerivastatin/Statin_ceriv/2'>binds HMGR</scene> via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Fluvastatin contribute to binding as well.<ref>PMID:11349148</ref> These interactions help Cerivastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.<ref>PMID:7784310</ref>
</StructureSection>
===Pharmacokinetics===
===Pharmacokinetics===
{| class="wikitable" border="1" width="48%" style="text-align:center"
<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">  
|-
<tr>
!  colspan="7" align="center"| Statin [[Pharmacokinetics]] at 10mg Dosage.<ref>PMID:11907637</ref><ref>PMID:15198967</ref><ref>PMID:12686673</ref><ref>PMID:18176327</ref><ref>PMID: 17452418</ref><ref>PMID:12895195</ref>
<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
|-
<div style="height:100%; width: 100%">
! Parameter
{{:Statin Pharmacokinetics}}
! [[Atorvastatin]] (Lipitor)
</div>
! [[Fluvastatin]] (Lescol)
</td>
! [[Lovastatin]] (Mevacor)
</tr>
! [[Simvastatin]] (Zocor)
</table>
! [[Rosuvastatin]] (Crestor)
! [[Cerivastatin]] (Baycol)
|-
! [[Pharmacokinetics#Tmax|T<sub>max</sub>]] (hr)
! 2.5
! 1
! 3
! 1.5
! 4
! 1.5
|-
! [[Pharmacokinetics#Cmax|C<sub>max</sub>]] (ng/ml)
! 27-66
! 448
! 10-20
! 7.3
! 4.34
! 3.43
|-
! [[Pharmacokinetics#Bioavailability_.28F.29|Bioavailability]] (%)
! 12
! 19-29
! 5
! 5
! 20
! 60
|-
! [[Pharmacokinetics#Protein_Binding|Protein Binding]] (%)
! 80-90
! 99
! 95
! 95
! 88
! 99
|-
! [[Pharmacokinetics#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
! 15-30
! 2
! 3
! 2.7
! 19
! 2.2
|-
! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
! 104
! ~150
! 33
! 125
! 48
! 14.5
|-
! [[Pharmacokinetics#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM)
! 154
! 198
! 800-4200
! 66
! 320
! 50-90
|-
! Equivalent LDL Reduction Dosage (mg)
! 10
! --
! 80
! 20
! 5
! --
|-
! Metabolism
! Hepatic <br/>(CYP3A4)
! Hepatic <br/>(CYP2C9)
! Hepatic <br/>(CYP3A4)
! Hepatic <br/>(CYP3A4)
! Not <br/>Metabolized
! Hepatic <br />(CYP2C8)
|}


===References===
===References===

Latest revision as of 15:33, 10 January 2024

Better Known as: Baycol

  • Marketed By: Bayer Healthcare
  • Major Indication: Hyperlipidemia & High Cholesterol (Hypercholesterolemia)
  • Drug Class: HMGR Inhibitor or Statin
  • Date of FDA Approval (Withdrawn): 1997 (2001)
  • 2000 Sales: $587 Million
  • Importance: An extremely well selling statin, but withdrawn in 2001 due to a high incidence of rhabdomyolysis. Statins are so ubiquitous, doctors have even suggested handing them out with fast food. See: the article
  • See Pharmaceutical Drugs for more information about other drugs and disorders

Mechanism of Action

Cerivastatin is an inhibitor of HMG-CoA Reductase (HMGR), a highly responsible for the committed step in cholesterol synthesis.[1] Cerivastatin, like most of the statins, via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Fluvastatin contribute to binding as well.[2] These interactions help Cerivastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.[3]

Cerivastatin, also known as Baycol

Drag the structure with the mouse to rotate

Pharmacokinetics

Statin Pharmacokinetics at 10mg Dosage
Parameter Atorvastatin (Lipitor) Fluvastatin (Lescol) Lovastatin (Mevacor) Simvastatin (Zocor) Rosuvastatin (Crestor) Cerivastatin (Baycol)
Tmax (hr) 2.5 1 3 1.5 4 1.5
Cmax (ng/ml) 27-66 448 10-20 7.3 4.34 3.43
Bioavailability (%) 12 19-29 5 5 20 60
Protein Binding (%) 80-90 99 95 95 88 99
T1/2 (hr) 15-30 2 3 2.7 19 2.2
AUC (ng/ml/hr) 104 ~150 33 125 48 14.5
IC50 (nM) 154 198 800 66 320 50-90
Equivalent LDL Reduction Dosage (mg) 10 -- 80 20 5 --
Metabolism Hepatic
(CYP3A4) 		Hepatic
(CYP2C9) 		Hepatic
(CYP3A4) 		Hepatic
(CYP3A4) 		None Hepatic
(CYP2C8)

For References, See References

References

  1. ↑ Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res. 1995 Jan;31(1):9-27. PMID:7784310
  2. ↑ Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001 May 11;292(5519):1160-4. PMID:11349148 doi:10.1126/science.1059344
  3. ↑ Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res. 1995 Jan;31(1):9-27. PMID:7784310


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David Canner, Alexander Berchansky
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