MK-2048 - Revision history

David Canner at 09:22, 10 December 2010

David Canner — Fri, 10 Dec 2010 09:22:59 GMT

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

	===Pharmacokinetics===		===Pharmacokinetics===
-	~~{\| class~~="~~wikitable~~" ~~border~~="1" width="53%" 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 11:33, 9 December 2010

David Canner — Thu, 09 Dec 2010 11:33:22 GMT

←Older revision		Revision as of 11:33, 9 December 2010
Line 7:		Line 7:
	* Projected Sales: N/A		* Projected Sales: N/A
	* Importance: It is a second generation [[Retroviral Integrase]] inhibitor expected to be the next effective HIV treatment to come to market. Clinical trials reveal that it is superior to [[Raltegravir]] with a nearly 4 times longer inhibition period.		* Importance: It is a second generation [[Retroviral Integrase]] inhibitor expected to be the next effective HIV treatment to come to market. Clinical trials reveal that it is superior to [[Raltegravir]] with a nearly 4 times longer inhibition period.
-	* ~~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="53%" 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 10:04:20 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='MK-2048/Integrase/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='MK-2048/Integrase_b/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. MK-2048 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='MK-2048/Integrase_ba/2'>MK-2048 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>	+	[[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='MK-2048/Integrase/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='MK-2048/Integrase_b/1'>binding the polynucleotides</scene> precisely within an active site, in close proximity to the predicted target DNA into which the viral DNA will be inserted. MK-2048 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='MK-2048/Integrase_ba/2'>MK-2048 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 10:03, 8 December 2010

David Canner — Wed, 08 Dec 2010 10:03:15 GMT

←Older revision		Revision as of 10:03, 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='MK-2048/Integrase/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='MK-2048/Integrase_b/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. MK-2048 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='MK-2048/Integrase_ba/2'>MK-2048 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='MK-2048/Integrase/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='MK-2048/Integrase_b/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. MK-2048 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='MK-2048/Integrase_ba/2'>MK-2048 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 10:02, 8 December 2010

David Canner — Wed, 08 Dec 2010 10:02:41 GMT

←Older revision		Revision as of 10:02, 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='MK-2048/Integrase/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='MK-2048/Integrase_b/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~~ 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='MK-2048/Integrase/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='MK-2048/Integrase_b/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. MK-2048 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='MK-2048/Integrase_ba/2'>MK-2048 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 09:54, 8 December 2010

David Canner — Wed, 08 Dec 2010 09:54:19 GMT

←Older revision		Revision as of 09:54, 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='~~___~~'>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. 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 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='MK-2048/Integrase/1'>complexes with viral DNA</scene>. The integrase domains interact extensively with the viral DNA, <scene name='MK-2048/Integrase_b/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 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 09:49, 8 December 2010

David Canner — Wed, 08 Dec 2010 09:49:13 GMT

←Older revision		Revision as of 09:49, 8 December 2010
Line 5:		Line 5:
	* Drug Class: [[Retroviral Integrase]] Inhibitor		* Drug Class: [[Retroviral Integrase]] Inhibitor
	* Expected FDA Approval: N/A (Currently in Phase III trials)		* Expected FDA Approval: N/A (Currently in Phase III trials)
-	* Projected ~~2013~~ Sales: N/A	+	* Projected Sales: N/A
	* Importance: It is a second generation [[Retroviral Integrase]] inhibitor expected to be the next effective HIV treatment to come to market. Clinical trials reveal that it is superior to [[Raltegravir]] with a nearly 4 times longer inhibition period.		* Importance: It is a second generation [[Retroviral Integrase]] inhibitor expected to be the next effective HIV treatment to come to market. Clinical trials reveal that it is superior to [[Raltegravir]] with a nearly 4 times longer inhibition period.
	* 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

David Canner at 09:27, 8 December 2010

David Canner — Wed, 08 Dec 2010 09:27:41 GMT

←Older revision		Revision as of 09:27, 8 December 2010
Line 1:		Line 1:
-	<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="The Investigational New Drug, MK-2048, ([[3oyj]])"/>	+	<applet load="" size="480" color="" frame="true" spin="on" Scene ="MK-2048/Mk-2048/1" align="right" caption="The Investigational New Drug, MK-2048, ([[3oyj]])"/>
	===Better Known as: N/A===		===Better Known as: N/A===
	* Marketed By: Merck & Co.		* Marketed By: Merck & Co.

David Canner: New page: ===Better Known as: N/A=== * Marketed By...
David Canner — Wed, 08 Dec 2010 09:07:07 GMT

New page: <applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="The Investigational New Drug, MK-2048, (3oyj)"/> ===Better Known as: N/A=== * Marketed By...

New page
<applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="The Investigational New Drug, MK-2048, ([[3oyj]])"/>
===Better Known as: N/A===
* Marketed By: Merck & Co.
* Major Indication: [[Human Immunodeficiency Virus]] Infection
* Drug Class: [[Retroviral Integrase]] Inhibitor
* Expected FDA Approval: N/A (Currently in Phase III trials)
* Projected 2013 Sales: N/A
* Importance: It is a second generation [[Retroviral Integrase]] inhibitor expected to be the next effective HIV treatment to come to market. Clinical trials reveal that it is superior to [[Raltegravir]] with a nearly 4 times longer inhibition period.
* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information

===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='_'>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. 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 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===
{| 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>
|-
! Parameter
! [[Raltegravir]]
! [[Elvitegravir]]
! [[MK-2048]]
|-
! [[Pharmaceutical_Drugs#Tmax|Tmax]] (hr)
! 1.8
! 2-4
! N/A
|-
! [[Pharmaceutical_Drugs#Cmax|Cmax]] (ng/ml)
! 4253
! 2070
! N/A
|-
! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
! 32
! ~30
! N/A
|-
! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
! 83
! N/A
! N/A
|-
! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T1/2]] (hr)
! 10.8
! 7.6
! N/A
|-
! [[Pharmaceutical_Drugs#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/>
NOEDITSECTION
NOTOC