Ritonavir - Revision history

Eric Martz at 15:31, 28 December 2023

Eric Martz — Thu, 28 Dec 2023 15:31:18 GMT

←Older revision		Revision as of 15:31, 28 December 2023
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	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>		</StructureSection>
		+	===See Also===
		+	* The page [[Molecular Playground/HIV Protease Inhibitor]] summarizes the history of AIDS before Ritonavir and the impact of Ritonavir and other [[HIV protease]] inhibitors.
		+
	===Pharmacokinetics===		===Pharmacokinetics===
	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">		<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">

Alexander Berchansky at 14:02, 27 December 2023

Alexander Berchansky — Wed, 27 Dec 2023 14:02:07 GMT

←Older revision		Revision as of 14:02, 27 December 2023
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-	<~~applet~~ load="" size=~~"450" color~~=~~"" frame="true" spin="on" Scene ="Ritonavir/Ritonavir/1" align="~~right" caption="Ritonavir, better known as Norvir, ([[1hxw]])"/>	+	<StructureSection load='' size='340' side='right' caption='Ritonavir, better known as Norvir, ([[1hxw]])' scene='Ritonavir/Ritonavir/1'>
	===Better Known as: Norvir (Kaletra when used in combination with Lopinavir)===		===Better Known as: Norvir (Kaletra when used in combination with Lopinavir)===
	* Marketed By: Abbott Laboratories<br />		* Marketed By: Abbott Laboratories<br />
Line 17:		Line 17:
	===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 09:10, 10 December 2010

David Canner — Fri, 10 Dec 2010 09:10:19 GMT

←Older revision		Revision as of 09:10, 10 December 2010
Line 1:		Line 1:
-	<applet load="" size="~~480~~" color="" frame="true" spin="on" Scene ="Ritonavir/Ritonavir/1" align="right" caption="Ritonavir, better known as Norvir, ([[1hxw]])"/>	+	<applet load="" size="450" color="" frame="true" spin="on" Scene ="Ritonavir/Ritonavir/1" align="right" caption="Ritonavir, better known as Norvir, ([[1hxw]])"/>
	===Better Known as: Norvir (Kaletra when used in combination with Lopinavir)===		===Better Known as: Norvir (Kaletra when used in combination with Lopinavir)===
	* Marketed By: Abbott Laboratories<br />		* Marketed By: Abbott Laboratories<br />

David Canner at 09:08, 10 December 2010

David Canner — Fri, 10 Dec 2010 09:08:53 GMT

←Older revision		Revision as of 09:08, 10 December 2010
Line 19:		Line 19:

	===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 11:29, 9 December 2010

David Canner — Thu, 09 Dec 2010 11:29:06 GMT

←Older revision		Revision as of 11:29, 9 December 2010
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	* U.S. 2009 Sales: $310 Million		* U.S. 2009 Sales: $310 Million
	* Importance: It is a powerful [[HIV Protease]] inhibitor. It is a major component of most HIV combination therapies because of its potent inhibition capacity of CYP3A4, increasing the bioavailability of other viral inhibitors.		* Importance: It is a powerful [[HIV Protease]] inhibitor. It is a major component of most HIV combination therapies because of its potent inhibition capacity of CYP3A4, increasing the bioavailability of other viral inhibitors.
-	* ~~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===
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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 47:		Line 47:
	! 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 59:		Line 59:
	! 4701		! 4701
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Bioavailability_.28F.29\|Bioavailability]] (%)	+	! [[Pharmacokinetics#Bioavailability_.28F.29\|Bioavailability]] (%)
	! --		! --
	! --		! --
Line 71:		Line 71:
	! 20-80		! 20-80
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Protein_Binding\|Protein Binding]] (%)	+	! [[Pharmacokinetics#Protein_Binding\|Protein Binding]] (%)
	! 99		! 99
	! >99		! >99
Line 83:		Line 83:
	! 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 95:		Line 95:
	! 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 107:		Line 107:
	! 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 09:08, 5 December 2010

David Canner — Sun, 05 Dec 2010 09:08:42 GMT

←Older revision		Revision as of 09:08, 5 December 2010
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	<applet load="" size="480" color="" frame="true" spin="on" Scene ="Ritonavir/Ritonavir/1" align="right" caption="Ritonavir, better known as Norvir, ([[1hxw]])"/>		<applet load="" size="480" color="" frame="true" spin="on" Scene ="Ritonavir/Ritonavir/1" align="right" caption="Ritonavir, better known as Norvir, ([[1hxw]])"/>
	===Better Known as: Norvir (Kaletra when used in combination with Lopinavir)===		===Better Known as: Norvir (Kaletra when used in combination with Lopinavir)===
-	* Marketed By: Abbott ~~Labs~~<br />	+	* Marketed By: Abbott Laboratories<br />
	* Major Indication: [[Human Immunodeficiency Virus]] Infection<br />		* Major Indication: [[Human Immunodeficiency Virus]] Infection<br />
	* Drug Class: [[HIV Protease]] Inhibitor		* Drug Class: [[HIV Protease]] Inhibitor

David Canner at 08:09, 5 December 2010

David Canner — Sun, 05 Dec 2010 08:09:12 GMT

←Older revision		Revision as of 08:09, 5 December 2010
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	* Drug Class: [[HIV Protease]] Inhibitor		* Drug Class: [[HIV Protease]] Inhibitor
	* Date of FDA Approval (Patent Expiration): 1996 (2013) <br />		* Date of FDA Approval (Patent Expiration): 1996 (2013) <br />
-	* 2009 Sales: $310 Million	+	* U.S. 2009 Sales: $310 Million
	* Importance: It is a powerful [[HIV Protease]] inhibitor. It is a major component of most HIV combination therapies because of its potent inhibition capacity of CYP3A4, increasing the bioavailability of other viral inhibitors.		* Importance: It is a powerful [[HIV Protease]] inhibitor. It is a major component of most HIV combination therapies because of its potent inhibition capacity of CYP3A4, increasing the bioavailability of other viral inhibitors.
	* 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 07:21, 5 December 2010

David Canner — Sun, 05 Dec 2010 07:21:48 GMT

←Older revision		Revision as of 07:21, 5 December 2010
Line 10:		Line 10:

	===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='Ritonavir/Prot/3'>HIV Protease</scene> come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Buried within this tunnel lies <scene name='Ritonavir/Cat/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Ritonavir/Cat/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the viral polyproteins. ~~Saquinavir~~ <scene name='Ritonavir/Cat/3'>binds very precisely</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 functional 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>PMID:17243183</ref>	+	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='Ritonavir/Prot/3'>HIV Protease</scene> come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Buried within this tunnel lies <scene name='Ritonavir/Cat/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Ritonavir/Cat/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the viral polyproteins. Ritonavir <scene name='Ritonavir/Cat/3'>binds very precisely</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 functional 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>PMID:17243183</ref>

David Canner at 06:37, 5 December 2010

David Canner — Sun, 05 Dec 2010 06:37:11 GMT

←Older revision		Revision as of 06:37, 5 December 2010
Line 11:		Line 11:
	===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='Ritonavir/Prot/3'>HIV Protease</scene> come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Buried within this tunnel lies <scene name='Ritonavir/Cat/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Ritonavir/Cat/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the viral polyproteins. Saquinavir <scene name='Ritonavir/Cat/3'>binds very precisely</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 functional 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>PMID:17243183</ref>		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='Ritonavir/Prot/3'>HIV Protease</scene> come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Buried within this tunnel lies <scene name='Ritonavir/Cat/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Ritonavir/Cat/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the viral polyproteins. Saquinavir <scene name='Ritonavir/Cat/3'>binds very precisely</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 functional 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>PMID:17243183</ref>
		+

	Despite its ability to inhibit HIV Protease, Ritonavir is primarily used in combination therapies to inhibit the metabolizing enzyme, <scene name='Ritonavir/Ritonavir_cyp/2'>cytochrome P4503A4</scene> (CYP3A4). Ritonair binds with <scene name='Ritonavir/Ritonavir_c/2'>high affinity to CYP3A4</scene>, inhibiting it. Since it is this enzyme which is responsible for metabolizing the other HIV Protease inhibitors, Ritonavir's inhibition of CYP3A4 increases the bioavilaibility of other [[Pharmaceutical_Drugs#Treatments\|antiviral medications]].<ref>PMID: 20937904</ref>		Despite its ability to inhibit HIV Protease, Ritonavir is primarily used in combination therapies to inhibit the metabolizing enzyme, <scene name='Ritonavir/Ritonavir_cyp/2'>cytochrome P4503A4</scene> (CYP3A4). Ritonair binds with <scene name='Ritonavir/Ritonavir_c/2'>high affinity to CYP3A4</scene>, inhibiting it. Since it is this enzyme which is responsible for metabolizing the other HIV Protease inhibitors, Ritonavir's inhibition of CYP3A4 increases the bioavilaibility of other [[Pharmaceutical_Drugs#Treatments\|antiviral medications]].<ref>PMID: 20937904</ref>

David Canner at 06:37, 5 December 2010

David Canner — Sun, 05 Dec 2010 06:37:01 GMT

←Older revision		Revision as of 06:37, 5 December 2010
Line 12:		Line 12:
	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='Ritonavir/Prot/3'>HIV Protease</scene> come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Buried within this tunnel lies <scene name='Ritonavir/Cat/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Ritonavir/Cat/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the viral polyproteins. Saquinavir <scene name='Ritonavir/Cat/3'>binds very precisely</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 functional 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>PMID:17243183</ref>		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='Ritonavir/Prot/3'>HIV Protease</scene> come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Buried within this tunnel lies <scene name='Ritonavir/Cat/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Ritonavir/Cat/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the viral polyproteins. Saquinavir <scene name='Ritonavir/Cat/3'>binds very precisely</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 functional 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>PMID:17243183</ref>

-	Despite its ability to inhibit HIV Protease, Ritonavir is primarily used in combination therapies to inhibit the metabolizing enzyme, cytochrome P4503A4. Ritonair binds with high affinity to CYP3A4, inhibiting it. Since it is this enzyme which is responsible for metabolizing the other HIV Protease inhibitors, Ritonavir's inhibition of CYP3A4 increases the bioavilaibility of other [[Pharmaceutical_Drugs#Treatments\|antiviral medications]].<ref>PMID: 20937904</ref>	+	Despite its ability to inhibit HIV Protease, Ritonavir is primarily used in combination therapies to inhibit the metabolizing enzyme, <scene name='Ritonavir/Ritonavir_cyp/2'>cytochrome P4503A4</scene> (CYP3A4). Ritonair binds with <scene name='Ritonavir/Ritonavir_c/2'>high affinity to CYP3A4</scene>, inhibiting it. Since it is this enzyme which is responsible for metabolizing the other HIV Protease inhibitors, Ritonavir's inhibition of CYP3A4 increases the bioavilaibility of other [[Pharmaceutical_Drugs#Treatments\|antiviral medications]].<ref>PMID: 20937904</ref>

	===Drug Resistance===		===Drug Resistance===