Amprenavir - Revision history

Alexander Berchansky at 13:37, 10 January 2024

Alexander Berchansky — Wed, 10 Jan 2024 13:37:56 GMT

←Older revision		Revision as of 13:37, 10 January 2024
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	<StructureSection load='' size='340' side='right' caption='Amprenavir, better known as Agenerase, ([[3nu4]])' scene='Amprenavir/Amprenavi/2'>		<StructureSection load='' size='340' side='right' caption='Amprenavir, better known as Agenerase, ([[3nu4]])' scene='Amprenavir/Amprenavi/2'>
-	<applet load="" size="450" color="" frame="true" spin="on" Scene ="Amprenavir/Amprenavi/2" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>
	===Better Known as: Agenerase===		===Better Known as: Agenerase===
	* Marketed By: GlaxoSmithKline<br />		* Marketed By: GlaxoSmithKline<br />

Alexander Berchansky at 13:37, 10 January 2024

Alexander Berchansky — Wed, 10 Jan 2024 13:37:37 GMT

←Older revision		Revision as of 13:37, 10 January 2024
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		+	<StructureSection load='' size='340' side='right' caption='Amprenavir, better known as Agenerase, ([[3nu4]])' scene='Amprenavir/Amprenavi/2'>
	<applet load="" size="450" color="" frame="true" spin="on" Scene ="Amprenavir/Amprenavi/2" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>		<applet load="" size="450" color="" frame="true" spin="on" Scene ="Amprenavir/Amprenavi/2" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>
	===Better Known as: Agenerase===		===Better Known as: Agenerase===
Line 14:		Line 15:
	===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===
	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">		<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">

David Canner at 09:11, 10 December 2010

David Canner — Fri, 10 Dec 2010 09:11:05 GMT

←Older revision		Revision as of 09:11, 10 December 2010
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-	<applet load="" size="~~480~~" color="" frame="true" spin="on" Scene ="Amprenavir/Amprenavi/2" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>	+	<applet load="" size="450" color="" frame="true" spin="on" Scene ="Amprenavir/Amprenavi/2" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>
	===Better Known as: Agenerase===		===Better Known as: Agenerase===
	* Marketed By: GlaxoSmithKline<br />		* Marketed By: GlaxoSmithKline<br />

David Canner at 09:05, 10 December 2010

David Canner — Fri, 10 Dec 2010 09:05:10 GMT

←Older revision		Revision as of 09:05, 10 December 2010
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	===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 [[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]]~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Tmax\|T<sub>max~~</~~sub~~>~~]] (hr)~~	+
-	~~! 4.4~~	+
-	~~! ~3~~	+
-	~~! 1.5~~	+
-	~~! 3.7~~	+
-	~~! .98~~	+
-	~~! 1.5-4~~	+
-	~~! 2~~	+
-	~~! .5~~	+
-	~~! 2-4~~	+
-	~~! 3.1~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Cmax\|C<sub>max~~</~~sub~~>~~]] (ng/ml)~~	+
-	~~! 13120~~	+
-	~~! 14600~~	+
-	~~! 8100~~	+
-	~~! 2297~~	+
-	~~! 4901~~	+
-	~~! 4820~~	+
-	~~! 11.9~~	+
-	~~! 2730~~	+
-	~~! ~4393~~	+
-	~~! 4701~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Bioavailability_.28F.29\|Bioavailability]] (%)~~	+
-	~~! --~~	+
-	~~! --~~	+
-	~~! 65~~	+
-	~~! 4~~	+
-	~~! --~~	+
-	~~! --~~	+
-	~~! --~~	+
-	~~! --~~	+
-	~~! 68~~	+
-	~~! 20-80~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Protein_Binding\|Protein Binding]] (%)~~	+
-	~~! 99~~	+
-	~~! >99~~	+
-	~~! 61~~	+
-	~~! 98~~	+
-	~~! 90~~	+
-	~~! 90~~	+
-	~~! 99~~	+
-	~~! 95~~	+
-	~~! 86~~	+
-	~~! 98~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#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~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)~~	+
-	~~! 128100~~	+
-	~~! 46500~~	+
-	~~! 20900~~	+
-	~~! 13467~~	+
-	~~! 11999~~	+
-	~~! 35000~~	+
-	~~! 117600~~	+
-	~~! 4746~~	+
-	~~! ~26045~~	+
-	~~! 31906~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#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===

David Canner at 11:24, 9 December 2010

David Canner — Thu, 09 Dec 2010 11:24:21 GMT

←Older revision		Revision as of 11:24, 9 December 2010
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	* 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===
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	{\| class="wikitable" border="1" width="52%" style="text-align:center"		{\| class="wikitable" border="1" width="52%" style="text-align:center"
	\|-		\|-
-	! 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>	+	! colspan="12" align="center"\| HIV Protease Inhibitor [[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>
	\|-		\|-
	! Parameter		! Parameter
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	! [[Nelfinavir]]		! [[Nelfinavir]]
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Tmax\|T<sub>max</sub>]] (hr)	+	! [[Pharmacokinetics#Tmax\|T<sub>max</sub>]] (hr)
	! 4.4		! 4.4
	! ~3		! ~3
Line 44:		Line 44:
	! 3.1		! 3.1
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Cmax\|C<sub>max</sub>]] (ng/ml)	+	! [[Pharmacokinetics#Cmax\|C<sub>max</sub>]] (ng/ml)
	! 13120		! 13120
	! 14600		! 14600
Line 56:		Line 56:
	! 4701		! 4701
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Bioavailability_.28F.29\|Bioavailability]] (%)	+	! [[Pharmacokinetics#Bioavailability_.28F.29\|Bioavailability]] (%)
	! --		! --
	! --		! --
Line 68:		Line 68:
	! 20-80		! 20-80
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Protein_Binding\|Protein Binding]] (%)	+	! [[Pharmacokinetics#Protein_Binding\|Protein Binding]] (%)
	! 99		! 99
	! >99		! >99
Line 80:		Line 80:
	! 98		! 98
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Half_Life_.28T1.2F2.29\|T<sub>1/2</sub>]] (hr)	+	! [[Pharmacokinetics#Half_Life_.28T1.2F2.29\|T<sub>1/2</sub>]] (hr)
	! 4.8		! 4.8
	! 4.2		! 4.2
Line 92:		Line 92:
	! 3.3		! 3.3
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)	+	! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)
	! 128100		! 128100
	! 46500		! 46500
Line 104:		Line 104:
	! 31906		! 31906
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Clearance_.28Cl.29\|Clearance]] (L/h)	+	! [[Pharmacokinetics#Clearance_.28Cl.29\|Clearance]] (L/h)
	! ~8.4		! ~8.4
	! 32.4		! 32.4

David Canner at 12:01, 5 December 2010

David Canner — Sun, 05 Dec 2010 12:01:20 GMT

←Older revision		Revision as of 12:01, 5 December 2010
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	===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===

David Canner at 11:53, 5 December 2010

David Canner — Sun, 05 Dec 2010 11:53:17 GMT

←Older revision		Revision as of 11:53, 5 December 2010
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-	<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>	+	<applet load="" size="480" color="" frame="true" spin="on" Scene ="Amprenavir/Amprenavi/2" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>
	===Better Known as: Agenerase===		===Better Known as: Agenerase===
	* Marketed By: GlaxoSmithKline<br />		* Marketed By: GlaxoSmithKline<br />

David Canner at 11:52, 5 December 2010

David Canner — Sun, 05 Dec 2010 11:52:55 GMT

←Older revision		Revision as of 11:52, 5 December 2010
Line 1:		Line 1:
-	<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="Amprenavir, better known as Agenerase, ([[~~3nu3~~]])"/>	+	<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>
	===Better Known as: Agenerase===		===Better Known as: Agenerase===
	* Marketed By: GlaxoSmithKline<br />		* Marketed By: GlaxoSmithKline<br />

David Canner at 11:38, 5 December 2010

David Canner — Sun, 05 Dec 2010 11:38:44 GMT

←Older revision		Revision as of 11:38, 5 December 2010
Line 1:		Line 1:
-	<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="Amprenavir, better known as Agenerase, ([[~~2o4p~~]])"/>	+	<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu3]])"/>
	===Better Known as: Agenerase===		===Better Known as: Agenerase===
	* Marketed By: GlaxoSmithKline<br />		* Marketed By: GlaxoSmithKline<br />

David Canner at 11:37, 5 December 2010

David Canner — Sun, 05 Dec 2010 11:37:57 GMT

←Older revision		Revision as of 11:37, 5 December 2010
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	* Drug Class: [[HIV Protease]] Inhibitor		* Drug Class: [[HIV Protease]] Inhibitor
	* Date of FDA Approval (Discontinued): 1999 (2004) <br />		* Date of FDA Approval (Discontinued): 1999 (2004) <br />
-	* ~~2009~~ Sales: ~~N/A~~	+	* 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		* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information