Amprenavir: Difference between revisions

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<applet  load="" size="480" color="" frame="true"  spin="on" Scene ="" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu3]])"/>
<StructureSection load='' size='340' side='right' caption='Amprenavir, better known as Agenerase, ([[3nu4]])' scene='Amprenavir/Amprenavi/2'>
===Better Known as: Agenerase===
===Better Known as: Agenerase===
* Marketed By: GlaxoSmithKline<br />
* Marketed By: GlaxoSmithKline<br />
Line 7: Line 7:
* 2004 Sales: ~$50 Million
* 2004 Sales: ~$50 Million
* Importance: It was the first [[HIV Protease]] inhibitor which required only twice-a-day dosing as opposed to every 8 hours. It was replaced by a longer acting prodrug version called [[Fosamprenavir]].
* Importance: It was the first [[HIV Protease]] inhibitor which required only twice-a-day dosing as opposed to every 8 hours. It was replaced by a longer acting prodrug version called [[Fosamprenavir]].
* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information
* See [[Pharmaceutical Drugs]] for more information about other drugs and diseases.


===Mechanism of Action===
===Mechanism of Action===
When [[HIV]] infects a host, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by [[HIV Protease]]. The subunits of <scene name='Tipranavir/Prot/1'>HIV Protease</scene> come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Within this tunnel lies <scene name='Tipranavir/Cat/3'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Tipranavir/Catas/1'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Indinavir <scene name='Tipranavir/Bound/1'>binds with great specificity</scene> to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their infectuous form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.<ref>PMID:1799632</ref><ref>doi:10.1038/nrd1907</ref>
When [[HIV]] first infects someone, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by [[HIV Protease]]. The subunits of <scene name='Amprenavir/Protease/1'>HIV Protease</scene> come together to form a catalytic tunnel capable of tightly binding the nascent peptides and cleaving them into their mature, infectious form. Within this tunnel lies <scene name='Amprenavir/Proteasec/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Amprenavir/Proteasecas/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Amprenavir <scene name='Amprenavir/Bound/1'>binds specifically</scene> to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their infectious form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.<ref>PMID:1799632</ref><ref>doi:10.1038/nrd1907</ref>


===Drug Resistance===
===Drug Resistance===
The biggest difficulty with treating [[HIV]] is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to [[HIV Protease]], See: [[HIV Protease Inhibitor Resistance Profile]]
The biggest difficulty with treating [[HIV]] is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to [[HIV Protease]], See: [[HIV Protease Inhibitor Resistance Profile]]
 
</StructureSection>
===Pharmacokinetics===
===Pharmacokinetics===
{| class="wikitable" border="1" width="52%" style="text-align:center"
<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">  
|-
<tr>
!  colspan="12" align="center"| HIV Protease Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated|Pharmacokinetics]]<ref>PMID:20400409</ref><ref>Ferry et al, United States Patent US6147095, Pharmacia & Upjohn Company.</ref><ref>L. Veronese et al. Single-Dose Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Type 1 Protease Inhibitor, in Subjects with Normal or Impaired Hepatic  Function. Antimicrob Agents Chemother. 2000 April; 44(4): 821–826.</ref><ref>J. Ford, et al. Intracellular and Plasma Pharmacokinetics of Saquinavir-Ritonavir, Administered at 1,600/100 Milligrams Once Daily in Human Immunodeficiency Virus-Infected Patients. Antimicrob Agents Chemother. 2004 July; 48(7): 2388–2393.</ref><ref>PMID:10620574</ref><ref>PMID:16086644</ref><ref>PMID:19131522</ref><ref>PMID: 10952482</ref><ref>PMID:16338276</ref><ref>PMID:19729375</ref><ref>PMID:12668574</ref><ref>PMID:17255144</ref><ref>PMID:10858338</ref>
<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
|-
<div style="height:100%; width: 100%">
! Parameter
{{:HIV Protease Inhibitor Pharmacokinetics}}
! [[Ritonavir]]
</div>
! [[Tipranavir]]
</td>
! [[Indinavir]]
</tr>
! [[Saquinavir]]
</table>
! [[Amprenavir]]
! [[Fosamprenavir]]
! [[Lopinavir]]
! [[Darunavir]]
! [[Atazanavir]]
! [[Nelfinavir]]
|-
! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)
! 4.4
! ~3
! 1.5
! 3.7
! .98
! 1.5-4
! 2
! .5
! 2-4
! 3.1
|-
! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml)
! 13120
! 14600
! 8100
! 2297
! 4901
! 4820
! 11.9
! 2730
! ~4393
! 4701
|-
! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
! --
! --
! 65
! 4
! --
! --
! --
! --
! 68
! 20-80
|-
! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
! 99
! >99
! 61
! 98
! 90
! 90
! 99
! 95
! 86
! 98
|-
! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
! 4.8
! 4.2
! 1.2
! 4.5
! 5.5
! 7.7
! 6.1
! 29.4
! 5.3
! 3.3
|-
! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
! 128100
! 46500
! 20900
! 13467
! 11999
! 35000
! 117600
! 4746
! ~26045
! 31906
|-
! [[Pharmaceutical_Drugs#Clearance_.28Cl.29|Clearance]] (L/h)
! ~8.4
! 32.4
! 49.5
! 36.7
! 56.8
! 84.4
! 1.7
! 32.8
! 13.6
! 37.3
|-
! Dosage (mg)
! 600
! 600
! 800
! 1000
! 600
! 1400
! 280
! 400
! 400
! 1250
|-
! Metabolism
! Hepatic (CYP3A4 & CYP2C19)
! Hepatic (CYP3A4)
! Hepatic (CYP3A4)
! Hepatic (CYP3A4 & CYP3A5)
! Hepatic (CYP3A4)
! Hepatic (CYP3A4)
! Hepatic (CYP3A4)
! Hepatic (CYP3A4)
! Hepatic (CYP3A4)
! Hepatic (CYP3A4)
|}


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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky
Retrieved from "https://proteopedia.openfox.io/w/Amprenavir"