MK-2048: Difference between revisions

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David Canner

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 * 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.
-* 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===
-[[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 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===
-{| class="wikitable" border="1" width="60%" style="text-align:center"
+<table style="background: cellspacing="0px"  align="" cellpadding="0px" width="50%">
-|-
+<tr>
-!  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>
+<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>
-! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)
-! 1.8
-! 2-4
-! N/A
-|-
-! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (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|T<sub>1/2</sub>]] (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===