Rimantadine
From Proteopedia
(Difference between revisions)
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* 1994 Sales: N/A | * 1994 Sales: N/A | ||
* Importance: One of the the first treatments for [[Influenza]] Infections. Since 1994, nearly 100% of influenza viruses had developed resistance to rimantadine, and it is no longer recommended as a treatment for the flu. | * Importance: One of the the first treatments for [[Influenza]] Infections. Since 1994, nearly 100% of influenza viruses had developed resistance to rimantadine, and it is no longer recommended as a treatment for the flu. | ||
| - | * | + | * See [[Pharmaceutical Drugs]] for more information about other drugs and disorders. |
===Mechanism of Action=== | ===Mechanism of Action=== | ||
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{| class="wikitable" border="1" width="45%" style="text-align:center" | {| class="wikitable" border="1" width="45%" style="text-align:center" | ||
|- | |- | ||
| - | ! colspan="7" align="center"| M2 Proton Channel Inhibitor [[ | + | ! colspan="7" align="center"| M2 Proton Channel Inhibitor [[Pharmacokinetics]]<ref>PMID:3662473</ref><ref>PMID:17156962</ref> |
|- | |- | ||
! Parameter | ! Parameter | ||
| Line 21: | Line 21: | ||
! [[Amantadine]] | ! [[Amantadine]] | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Tmax|T<sub>max</sub>]] (hr) |
! 4.3 | ! 4.3 | ||
! 2.5 | ! 2.5 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Cmax|C<sub>max</sub>]] (ng/ml) |
! 310 | ! 310 | ||
! 402 | ! 402 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Bioavailability_.28F.29|Bioavailability]] (%) |
! >90 | ! >90 | ||
! >90 | ! >90 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Protein_Binding|Protein Binding]] (%) |
! 40 | ! 40 | ||
! 67 | ! 67 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr) |
! 27.7 | ! 27.7 | ||
! ~15 | ! ~15 | ||
|- | |- | ||
| - | ! [[ | + | ! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr) |
! 11917 | ! 11917 | ||
! 5420 | ! 5420 | ||
Revision as of 11:33, 9 December 2010
|
Better Known as: Flumadine
- Marketed By: Forest Labs
- Major Indication: Influenza Infection
- Drug Class: M2 Proton Channel Inhibitor
- Date of FDA Approval (Patent Expiration): 1993 (2001)
- 1994 Sales: N/A
- Importance: One of the the first treatments for Influenza Infections. Since 1994, nearly 100% of influenza viruses had developed resistance to rimantadine, and it is no longer recommended as a treatment for the flu.
- See Pharmaceutical Drugs for more information about other drugs and disorders.
Mechanism of Action
The Influenza A Virus viral envelope is dotted with various ion channels including M2 Proton Channels. The plays a critical role in the life cycle of the Influenza virus. It enables hydrogen ions to enter the virion form the endosome. The result of this is a more acidic environment within the virus, causing dissociation of the viral matrix protein M1 from the ribonucleoprotein RNP. Dissociation of the viral matrix protein is a crucial step in uncoating of the virus and exposing its contents to the cytoplasm of the host cell, allowing the virus to hijack the cellular machinery to replicate. outside the pore formed by the M2 protein, Leu 43, Leu 40, Asp 44, Arg 45, Trp 41 from one chain and Ile 42 from the neighboring chain. This effectively disables the protein from transferring protons into the viral particle.[1]
Pharmacokinetics
| M2 Proton Channel Inhibitor Pharmacokinetics[2][3] | ||||||
|---|---|---|---|---|---|---|
| Parameter | Rimantadine | Amantadine | ||||
| Tmax (hr) | 4.3 | 2.5 | ||||
| Cmax (ng/ml) | 310 | 402 | ||||
| Bioavailability (%) | >90 | >90 | ||||
| Protein Binding (%) | 40 | 67 | ||||
| T1/2 (hr) | 27.7 | ~15 | ||||
| AUC (ng/ml/hr) | 11917 | 5420 | ||||
| Dosage (mg) | 100 | 100 | ||||
| Metabolism | Negligible | Negligible | ||||
References
- ↑ Schnell JR, Chou JJ. Structure and mechanism of the M2 proton channel of influenza A virus. Nature. 2008 Jan 31;451(7178):591-5. PMID:18235503 doi:10.1038/nature06531
- ↑ Anderson EL, Van Voris LP, Bartram J, Hoffman HE, Belshe RB. Pharmacokinetics of a single dose of rimantadine in young adults and children. Antimicrob Agents Chemother. 1987 Jul;31(7):1140-2. PMID:3662473
- ↑ Wang P, Liang YZ, Chen BM, Zhou N, Yi LZ, Yu Y, Yi ZB. Quantitative determination of amantadine in human plasma by liquid chromatography-mass spectrometry and the application in a bioequivalence study. J Pharm Biomed Anal. 2007 Mar 12;43(4):1519-25. Epub 2006 Dec 6. PMID:17156962 doi:10.1016/j.jpba.2006.10.044
