Bevacizumab
From Proteopedia
(Difference between revisions)
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| - | <applet load="" size="480" color="" frame="true" spin="on" Scene =" | + | <applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="Bevacizumab, also known as Avastin"/> |
| - | ===Better Known as: | + | ===Better Known as: Avastin=== |
| - | * Marketed By: | + | * Marketed By: Genentech & Roche<br /> |
| - | * Major Indication: [[ | + | * Major Indication: Colorectal [[Cancer]]<br /> |
| - | * Drug Class: [[ | + | * Drug Class: [[VEGF]] Inhibitor - [[Monoclonal Antibody]] |
| - | * Date of FDA Approval (Patent Expiration): | + | * Date of FDA Approval (Patent Expiration): 2004 ( |
| - | * | + | * 2009 Sales: $4.8 Billion<ref>Irena Melnikova, Therapies for Alzheimer's disease, Nature Reviews Drug Discovery 6, 341-342 (May 2007)</ref> |
| - | * Importance: | + | * Importance: It is one of the best selling [[cancer]] treatments in history. Despite being effective against colorectal cancer, post-approval studies after accelerated approval revealed that Avastin was ineffective in treating breast cancer. Many question the $90,000/year bill to take Avastin when it extends life on average only 10 months. |
* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | * The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
| - | |||
| - | Rivastigmine is an [[Acetylcholinesterase]] (AChE) inhibitor. It binds to the active site of <scene name='Rivastigmine/Acetylcholinesterase/1'>AChE</scene>, utilizing many of the same residues which bind and break down acetylcholine. By inhibiting AChE, the important neurotransmitter, [[acetylcholine]], is degraded at a slower rate, helping reverse the marked decrease in neuronal function evident in [[Alzheimer's Disease]] patients. Rivastigmine is rapidly metabolized into its principal components (carbamyl and NAP moieties) which are powerful Acetylcholine inhibitors. These components primarily <scene name='Rivastigmine/Bound/1'>primarily interact with residues</scene> GLy 117, Gly 118, Gly 119 Ala 201, Trp 233, Phe 290, Trp 84, Phe 330, His 440, & Phe 288 in tightly binding to the AChE binding site via pi stacking and hydrogen bond interactions. Rivastigmine outcompetes acetylcholine for the active site of AChE, inhibiting the esterase<ref>PMID:11888271</ref> | ||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
{| class="wikitable" border="1" width="30%" style="text-align:center" | {| class="wikitable" border="1" width="30%" style="text-align:center" | ||
|- | |- | ||
| - | ! colspan="2" align="center"| VEGF Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated|Pharmacokinetics]] | + | ! colspan="2" align="center"| VEGF Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated|Pharmacokinetics]]<ref>PMID:17093010</ref> |
|- | |- | ||
! Parameter | ! Parameter | ||
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|- | |- | ||
! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml) | ! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml) | ||
| - | ! | + | ! 284000 |
|- | |- | ||
! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%) | ! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%) | ||
| - | ! | + | ! 100 |
|- | |- | ||
| - | + | ! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (days) | |
| - | + | ! 20 | |
| - | + | ||
| - | ! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] ( | + | |
| - | ! | + | |
|- | |- | ||
| - | ! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] ( | + | ! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ug/ml/hr) |
| - | ! | + | ! 97488 |
|- | |- | ||
! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM) | ! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM) | ||
| - | ! | + | ! .9 |
|- | |- | ||
! [[Pharmaceutical_Drugs#Clearance_.28Cl.29|Clearance]] (L/h) | ! [[Pharmaceutical_Drugs#Clearance_.28Cl.29|Clearance]] (L/h) | ||
| - | ! . | + | ! .0096 |
|- | |- | ||
! Dosage (mg/kg) | ! Dosage (mg/kg) | ||
! 10 | ! 10 | ||
| - | |- | ||
| - | ! Metabolism | ||
| - | ! [[Bevacizumab]] | ||
|} | |} | ||
Revision as of 11:35, 6 December 2010
|
Better Known as: Avastin
- Marketed By: Genentech & Roche
- Major Indication: Colorectal Cancer
- Drug Class: VEGF Inhibitor - Monoclonal Antibody
- Date of FDA Approval (Patent Expiration): 2004 (
- 2009 Sales: $4.8 Billion[1]
- Importance: It is one of the best selling cancer treatments in history. Despite being effective against colorectal cancer, post-approval studies after accelerated approval revealed that Avastin was ineffective in treating breast cancer. Many question the $90,000/year bill to take Avastin when it extends life on average only 10 months.
- The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information
Mechanism of Action
Pharmacokinetics
| VEGF Inhibitor Pharmacokinetics[2] | |
|---|---|
| Parameter | Bevacizumab |
| Tmax (hr) | 5.17 |
| Cmax (ng/ml) | 284000 |
| Bioavailability (%) | 100 |
| T1/2 (days) | 20 |
| AUC (ug/ml/hr) | 97488 |
| IC50 (nM) | .9 |
| Clearance (L/h) | .0096 |
| Dosage (mg/kg) | 10 |
References
- ↑ Irena Melnikova, Therapies for Alzheimer's disease, Nature Reviews Drug Discovery 6, 341-342 (May 2007)
- ↑ Garnier-Viougeat N, Rixe O, Paintaud G, Ternant D, Degenne D, Mouawad R, Deray G, Izzedine H. Pharmacokinetics of bevacizumab in haemodialysis. Nephrol Dial Transplant. 2007 Mar;22(3):975. Epub 2006 Nov 8. PMID:17093010 doi:10.1093/ndt/gfl664
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David Canner, Michal Harel, Joel L. Sussman, Alexander Berchansky
