Elvitegravir - Revision history

Alexander Berchansky at 14:19, 29 August 2023

Alexander Berchansky — Tue, 29 Aug 2023 14:19:41 GMT

←Older revision		Revision as of 14:19, 29 August 2023
Line 1:		Line 1:
-	<~~applet~~ load="" size=~~"480" color~~=~~"" frame="true" spin="on" Scene ="Elvitegravir/Elvitegravir/1" align="~~right" caption="The Investigational ~~New~~ Drug, Elvitegravir, ([[3l2u]])"/>	+	<StructureSection load='' size='340' side='right' caption='The Investigational Drug, Elvitegravir, ([[3l2u]])' scene='Elvitegravir/Elvitegravir/1'>
	===Better Known as: N/A===		===Better Known as: N/A===
	* Marketed By: Gilead Sciences		* Marketed By: Gilead Sciences
Line 23:		Line 23:
	</table>		</table>

		+	</StructureSection>
	===References===		===References===
	<references/>		<references/>
	__NOEDITSECTION__		__NOEDITSECTION__
	__NOTOC__		__NOTOC__

David Canner at 09:22, 10 December 2010

David Canner — Fri, 10 Dec 2010 09:22:44 GMT

←Older revision		Revision as of 09:22, 10 December 2010
Line 13:		Line 13:

	===Pharmacokinetics===		===Pharmacokinetics===
-	~~{\| class~~="~~wikitable~~" ~~border~~="1" width="55%" style="~~text~~-align:~~center~~"	+	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="50%">
-	\|-	+	<tr>
-	~~! colspan~~="4" ~~align="center"\|~~ Retroviral Integrase Inhibitor [[Pharmacokinetics~~]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.~~</~~ref><ref>doi: 10.1128/AAC.01543-07</ref~~>	+	<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">
-	\|-	+	<div style="height:100%; width: 100%">
-	~~! Parameter~~	+	{{:Retroviral Integrase Inhibitor Pharmacokinetics}}
-	~~! [[Raltegravir]]~~	+	</div>
-	~~! [[Elvitegravir]]~~	+	</td>
-	~~! [[MK-2048]]~~	+	</tr>
-	\|-	+	</table>
-	~~! [[Pharmacokinetics#Tmax\|T<sub>max~~</~~sub~~>~~]] (hr)~~	+
-	~~! 1.8~~	+
-	~~! 2-4~~	+
-	~~! N/A~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Cmax\|C<sub>max~~</~~sub~~>~~]] (ng/ml)~~	+
-	~~! 4253~~	+
-	~~! 2070~~	+
-	~~! N/A~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Bioavailability_.28F.29\|Bioavailability]] (%)~~	+
-	~~! 32~~	+
-	~~! ~30~~	+
-	~~! N/A~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Protein_Binding\|Protein Binding]] (%)~~	+
-	~~! 83~~	+
-	~~! N/A~~	+
-	~~! N/A~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Half_Life_.28T1.2F2.29\|T~~<~~sub>1~~/~~2</sub~~>~~]] (hr)~~	+
-	~~! 10.8~~	+
-	~~! 7.6~~	+
-	~~! N/A~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)~~	+
-	~~! 10168~~	+
-	~~! 21200~~	+
-	~~! N/A~~	+
-	\|-	+
-	~~! Dosage (mg)~~	+
-	~~! 400~~	+
-	~~! 150~~	+
-	~~! N/A~~	+
-	\|-	+
-	~~! Metabolism~~	+
-	~~! Hepatic - (UGT1A1)~~	+
-	~~! Hepatic - (CYP3A4)~~	+
-	~~! N/A~~	+
-	\|}	+

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

David Canner at 11:32, 9 December 2010

David Canner — Thu, 09 Dec 2010 11:32:37 GMT

←Older revision		Revision as of 11:32, 9 December 2010
Line 7:		Line 7:
	* Projected 2013 Sales: $460 Million		* Projected 2013 Sales: $460 Million
	* Importance: It is expected to be the next effective HIV treatment to come to market. Expected to be the second [[Retroviral Integrase]] inhibitor approved. Currently in phase III clinical trials. Results from phase II trials indicate that the once-daily treatment was more effective than current [[HIV Protease]] inhibitor combinations.<ref>PMID:17977962</ref>		* Importance: It is expected to be the next effective HIV treatment to come to market. Expected to be the second [[Retroviral Integrase]] inhibitor approved. Currently in phase III clinical trials. Results from phase II trials indicate that the once-daily treatment was more effective than current [[HIV Protease]] inhibitor combinations.<ref>PMID:17977962</ref>
-	* ~~The following is a list of Pharmacokinetic Parameters.~~ See: [[Pharmaceutical Drugs]] for more information	+	* See [[Pharmaceutical Drugs]] for more information about other drugs and disorders.

	===Mechanism of Action===		===Mechanism of Action===
Line 13:		Line 13:

	===Pharmacokinetics===		===Pharmacokinetics===
-	{\| class="wikitable" border="1" width="60%" style="text-align:center"	+	{\| class="wikitable" border="1" width="55%" style="text-align:center"
	\|-		\|-
-	! colspan="4" align="center"\| Retroviral Integrase Inhibitor [[~~Pharmaceutical_Drugs#Pharmacokinetics_Translated\|~~Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>	+	! colspan="4" align="center"\| Retroviral Integrase Inhibitor [[Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>
	\|-		\|-
	! Parameter		! Parameter
Line 22:		Line 22:
	! [[MK-2048]]		! [[MK-2048]]
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Tmax\|T<sub>max</sub>]] (hr)	+	! [[Pharmacokinetics#Tmax\|T<sub>max</sub>]] (hr)
	! 1.8		! 1.8
	! 2-4		! 2-4
	! N/A		! N/A
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Cmax\|C<sub>max</sub>]] (ng/ml)	+	! [[Pharmacokinetics#Cmax\|C<sub>max</sub>]] (ng/ml)
	! 4253		! 4253
	! 2070		! 2070
	! N/A		! N/A
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Bioavailability_.28F.29\|Bioavailability]] (%)	+	! [[Pharmacokinetics#Bioavailability_.28F.29\|Bioavailability]] (%)
	! 32		! 32
	! ~30		! ~30
	! N/A		! N/A
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Protein_Binding\|Protein Binding]] (%)	+	! [[Pharmacokinetics#Protein_Binding\|Protein Binding]] (%)
	! 83		! 83
	! N/A		! N/A
	! N/A		! N/A
	\|-		\|-
-	! [[~~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)
	! 10.8		! 10.8
	! 7.6		! 7.6
	! N/A		! N/A
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)	+	! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)
	! 10168		! 10168
	! 21200		! 21200

David Canner at 10:04, 8 December 2010

David Canner — Wed, 08 Dec 2010 10:04:57 GMT

←Older revision		Revision as of 10:04, 8 December 2010
Line 10:		Line 10:

	===Mechanism of Action===		===Mechanism of Action===
-	[[Retroviral Integrase]] is produced by the HIV retrovirus, enabling [[HIV]] to integrate its genetic material into the [[DNA]] of the infected cell. This integration step effectively transforms the infected cell into a permanent carrier of the viral genome, allowing the virus to persist and proliferate nearly without limit.<ref>PMID:17107277</ref> HIV retroviral integrase forms "intasomes" when it <scene name='Elvitegravir/Full/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='Elvitegravir/Tight/1'>binding the nucleotide chains</scene> precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. Elvitegravir binds with great specificity to the HIV integrase active site. It orients itself in such a way as to displace the reactive viral DNA end from the active site almost completely. <scene name='Elvitegravir/Tightasdf/2'>Elvitegravir binds</scene> to residues Asp 128, Asp 185, & Glu 221 via strong interactions with magnesium ions and has extensive π-stacking interactions with the final two nucleotide rings on one viral DNA strand. This disruption prevents the viral DNA from interacting with the target DNA, preventing integration and HIV proliferation.<ref>doi: 10.1038/nature08784</ref>	+	[[Retroviral Integrase]] is produced by the HIV retrovirus, enabling [[HIV]] to integrate its genetic material into the [[DNA]] of the infected cell. This integration step effectively transforms the infected cell into a permanent carrier of the viral genome, allowing the virus to persist and proliferate nearly without limit.<ref>PMID:17107277</ref> HIV retroviral integrase forms "intasomes" when it <scene name='Elvitegravir/Full/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='Elvitegravir/Tight/1'>binding the nucleotide chains</scene> precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. Elvitegravir binds with great specificity to the HIV integrase active site. It orients itself in such a way as to displace the reactive viral DNA end from the active site almost completely. <scene name='Elvitegravir/Tightasdf/2'>Elvitegravir binds</scene> to residues Asp 128, Asp 185, & Glu 221 via strong interactions with magnesium ions and has extensive π-stacking interactions with the final two nucleotide rings on one viral DNA strand. This disruption prevents the viral DNA from interacting with the target DNA, preventing integration and HIV proliferation.<ref>doi: 10.1038/nature08784</ref><ref>PMID:21030679</ref>

	===Pharmacokinetics===		===Pharmacokinetics===

David Canner at 08:57, 8 December 2010

David Canner — Wed, 08 Dec 2010 08:57:59 GMT

←Older revision		Revision as of 08:57, 8 December 2010
Line 13:		Line 13:

	===Pharmacokinetics===		===Pharmacokinetics===
-	{\| class="wikitable" border="1" width="55%" style="text-align:center"	+	{\| class="wikitable" border="1" width="60%" style="text-align:center"
	\|-		\|-
	! colspan="4" align="center"\| Retroviral Integrase Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated\|Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>		! colspan="4" align="center"\| Retroviral Integrase Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated\|Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>

David Canner at 08:57, 8 December 2010

David Canner — Wed, 08 Dec 2010 08:57:40 GMT

←Older revision		Revision as of 08:57, 8 December 2010
Line 13:		Line 13:

	===Pharmacokinetics===		===Pharmacokinetics===
-	{\| class="wikitable" border="1" width="50%" style="text-align:center"	+	{\| class="wikitable" border="1" width="55%" style="text-align:center"
	\|-		\|-
	! colspan="4" align="center"\| Retroviral Integrase Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated\|Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>		! colspan="4" align="center"\| Retroviral Integrase Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated\|Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>

David Canner at 08:57, 8 December 2010

David Canner — Wed, 08 Dec 2010 08:57:23 GMT

←Older revision		Revision as of 08:57, 8 December 2010
Line 13:		Line 13:

	===Pharmacokinetics===		===Pharmacokinetics===
-	{\| class="wikitable" border="1" width="45%" style="text-align:center"	+	{\| class="wikitable" border="1" width="50%" style="text-align:center"
	\|-		\|-
-	! colspan="12" align="center"\| Retroviral Integrase Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated\|Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>	+	! colspan="4" align="center"\| Retroviral Integrase Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated\|Pharmacokinetics]]<ref>A Gaur, et al. Pharmacokinetics and Safety of Once-Daily Elvitegravir in HIV-Infected Adolescents. 17th Conference on Retroviruses. Poster Number: 874.</ref><ref>doi: 10.1128/AAC.01543-07</ref>
	\|-		\|-
	! Parameter		! Parameter
	! [[Raltegravir]]		! [[Raltegravir]]
	! [[Elvitegravir]]		! [[Elvitegravir]]
		+	! [[MK-2048]]
	\|-		\|-
	! [[Pharmaceutical_Drugs#Tmax\|T<sub>max</sub>]] (hr)		! [[Pharmaceutical_Drugs#Tmax\|T<sub>max</sub>]] (hr)
	! 1.8		! 1.8
	! 2-4		! 2-4
		+	! N/A
	\|-		\|-
	! [[Pharmaceutical_Drugs#Cmax\|C<sub>max</sub>]] (ng/ml)		! [[Pharmaceutical_Drugs#Cmax\|C<sub>max</sub>]] (ng/ml)
	! 4253		! 4253
	! 2070		! 2070
		+	! N/A
	\|-		\|-
	! [[Pharmaceutical_Drugs#Bioavailability_.28F.29\|Bioavailability]] (%)		! [[Pharmaceutical_Drugs#Bioavailability_.28F.29\|Bioavailability]] (%)
	! 32		! 32
	! ~30		! ~30
		+	! N/A
	\|-		\|-
	! [[Pharmaceutical_Drugs#Protein_Binding\|Protein Binding]] (%)		! [[Pharmaceutical_Drugs#Protein_Binding\|Protein Binding]] (%)
	! 83		! 83
		+	! N/A
	! N/A		! N/A
	\|-		\|-
Line 40:		Line 45:
	! 10.8		! 10.8
	! 7.6		! 7.6
		+	! N/A
	\|-		\|-
	! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)		! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)
	! 10168		! 10168
	! 21200		! 21200
		+	! N/A
	\|-		\|-
	! Dosage (mg)		! Dosage (mg)
	! 400		! 400
	! 150		! 150
		+	! N/A
	\|-		\|-
	! Metabolism		! Metabolism
	! Hepatic - (UGT1A1)		! Hepatic - (UGT1A1)
	! Hepatic - (CYP3A4)		! Hepatic - (CYP3A4)
		+	! N/A
	\|}		\|}

David Canner at 08:55, 8 December 2010

David Canner — Wed, 08 Dec 2010 08:55:30 GMT

←Older revision		Revision as of 08:55, 8 December 2010
Line 10:		Line 10:

	===Mechanism of Action===		===Mechanism of Action===
-	[[Retroviral Integrase]] is produced by the HIV retrovirus, enabling [[HIV]] to integrate its genetic material into the [[DNA]] of the infected cell. This integration step effectively transforms the infected cell into a permanent carrier of the viral genome, allowing the virus to persist and proliferate ~~extensively~~.<ref>PMID:17107277</ref> HIV retroviral integrase forms "intasomes" when it <scene name='Elvitegravir/Full/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='Elvitegravir/Tight/1'>binding the nucleotide chains</scene> precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. ~~Raltegravir~~ binds with great specificity to the HIV integrase active site. It orients itself in such a way as to displace the reactive viral DNA end from the active site almost completely. <scene name='_'>~~Raltegravir~~ binds</scene> to residues Asp 128, Asp 185, & Glu 221 via ~~hydrogen bonds,~~ has extensive π-stacking interactions with ~~residues Tyr 212, Pro 214 and~~ the final two nucleotide rings on one viral DNA strand. This disruption prevents the viral DNA from interacting with the target DNA, preventing integration and HIV proliferation.<ref>doi: 10.1038/nature08784</ref>	+	[[Retroviral Integrase]] is produced by the HIV retrovirus, enabling [[HIV]] to integrate its genetic material into the [[DNA]] of the infected cell. This integration step effectively transforms the infected cell into a permanent carrier of the viral genome, allowing the virus to persist and proliferate nearly without limit.<ref>PMID:17107277</ref> HIV retroviral integrase forms "intasomes" when it <scene name='Elvitegravir/Full/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='Elvitegravir/Tight/1'>binding the nucleotide chains</scene> precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. Elvitegravir binds with great specificity to the HIV integrase active site. It orients itself in such a way as to displace the reactive viral DNA end from the active site almost completely. <scene name='Elvitegravir/Tightasdf/2'>Elvitegravir binds</scene> to residues Asp 128, Asp 185, & Glu 221 via strong interactions with magnesium ions and has extensive π-stacking interactions with the final two nucleotide rings on one viral DNA strand. This disruption prevents the viral DNA from interacting with the target DNA, preventing integration and HIV proliferation.<ref>doi: 10.1038/nature08784</ref>

	===Pharmacokinetics===		===Pharmacokinetics===

David Canner at 08:44, 8 December 2010

David Canner — Wed, 08 Dec 2010 08:44:01 GMT

←Older revision		Revision as of 08:44, 8 December 2010
Line 10:		Line 10:

	===Mechanism of Action===		===Mechanism of Action===
-	[[Retroviral Integrase]] is produced by the HIV retrovirus, enabling [[HIV]] to integrate its genetic material into the [[DNA]] of the infected cell. This integration step effectively transforms the infected cell into a permanent carrier of the viral genome, allowing the virus to persist and proliferate extensively.<ref>PMID:17107277</ref> HIV retroviral integrase forms "intasomes" when it <scene name='_'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='_'>binding the nucleotide chains</scene> precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. Raltegravir binds with great specificity to the HIV integrase active site. It orients itself in such a way as to displace the reactive viral DNA end from the active site almost completely. <scene name='_'>Raltegravir binds</scene> to residues Asp 128, Asp 185, & Glu 221 via hydrogen bonds, has extensive π-stacking interactions with residues Tyr 212, Pro 214 and the final two nucleotide rings on one viral DNA strand. This disruption prevents the viral DNA from interacting with the target DNA, preventing integration and HIV proliferation.<ref>doi: 10.1038/nature08784</ref>	+	[[Retroviral Integrase]] is produced by the HIV retrovirus, enabling [[HIV]] to integrate its genetic material into the [[DNA]] of the infected cell. This integration step effectively transforms the infected cell into a permanent carrier of the viral genome, allowing the virus to persist and proliferate extensively.<ref>PMID:17107277</ref> HIV retroviral integrase forms "intasomes" when it <scene name='Elvitegravir/Full/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='Elvitegravir/Tight/1'>binding the nucleotide chains</scene> precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. Raltegravir binds with great specificity to the HIV integrase active site. It orients itself in such a way as to displace the reactive viral DNA end from the active site almost completely. <scene name='_'>Raltegravir binds</scene> to residues Asp 128, Asp 185, & Glu 221 via hydrogen bonds, has extensive π-stacking interactions with residues Tyr 212, Pro 214 and the final two nucleotide rings on one viral DNA strand. This disruption prevents the viral DNA from interacting with the target DNA, preventing integration and HIV proliferation.<ref>doi: 10.1038/nature08784</ref>

	===Pharmacokinetics===		===Pharmacokinetics===

David Canner at 08:40, 8 December 2010

David Canner — Wed, 08 Dec 2010 08:40:30 GMT

←Older revision		Revision as of 08:40, 8 December 2010
Line 1:		Line 1:
-	<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="The Investigational New Drug, Elvitegravir, ([[3l2u]])"/>	+	<applet load="" size="480" color="" frame="true" spin="on" Scene ="Elvitegravir/Elvitegravir/1" align="right" caption="The Investigational New Drug, Elvitegravir, ([[3l2u]])"/>
	===Better Known as: N/A===		===Better Known as: N/A===
	* Marketed By: Gilead Sciences		* Marketed By: Gilead Sciences