Tipranavir: Difference between revisions

Latest revision as of 12:46, 11 January 2024

Better Known as: Aptivus

Marketed By: Boehringer-Ingelheim
Major Indication: Human Immunodeficiency Virus Infection
Drug Class: HIV Protease Inhibitor
Date of FDA Approval (Patent Expiration): 2005 (2015)
2009 Sales: N/A
Importance: It was the ninth HIV Protease inhibitor approved by the FDA for treatment of HIV. It is a very potent inhibitor, and is often recommended for patients who have become resistant to other treatments, but also has a relatively harsh side-effect profile.
See Pharmaceutical Drugs for more information about other drugs and diseases.

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 HIV Protease come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Within this tunnel lies two Asp-Thr-Gly conserved sequences, which contain the catalytic Asp residues. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Tipranavir binds with great specificity 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.^[1]^[2]

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

↑ Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie. 1991 Nov;73(11):1391-6. PMID:1799632
↑ Flexner C, Bate G, Kirkpatrick P. Tipranavir. Nat Rev Drug Discov. 2005 Dec;4(12):955-6. PMID:16370086 doi:10.1038/nrd1907

Pharmacokinetics

HIV Protease Inhibitor Human Immunodeficiency Virus
Parameter	HIV Protease	Tipranavir	HIV Protease	Pharmaceutical Drugs	HIV	HIV Protease	HIV	HIV Protease	HIV Protease Inhibitor Resistance Profile	Nelfinavir
T_max (hr)	4.4	~3	1.5	3.7	.98	1.5-4	2	.5	2-4	3.1
C_max (ng/ml)	13120	14600	8100	2297	4901	4820	11.9	2730	~4393	4701
Bioavailability (%)	--	--	65	4	--	--	--	--	68	20-80
Protein Binding (%)	99	>99	61	98	90	90	99	95	86	98
T_1/2 (hr)	4.8	4.2	1.2	4.5	5.5	7.7	6.1	29.4	5.3	3.3
AUC (ng/ml/hr)	128100	46500	20900	13467	11999	35000	117600	4746	~26045	31906
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)

For Pharmacokinetic Data References, See: References

References

Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky

[1] Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie. 1991 Nov;73(11):1391-6. PMID:1799632

[2] Flexner C, Bate G, Kirkpatrick P. Tipranavir. Nat Rev Drug Discov. 2005 Dec;4(12):955-6. PMID:16370086 doi:10.1038/nrd1907

[1]

[2]

@@ Line 1: / Line 1: @@
-<applet   load="" size="480" color="" frame="true"  spin="on" Scene ="Tipranavir/Tipranavir/1" align="right" caption="Tipranavir, better known as Aptivus, ([[2o4p]])"/>
+<StructureSection load='' size='340' side='right' caption='Tipranavir, better known as Aptivus, ([[2o4p]])' scene='Tipranavir/Tipranavir/1'>
 ===Better Known as: Aptivus===
 * Marketed By: Boehringer-Ingelheim<br />
@@ Line 7: / Line 7: @@
 * 2009 Sales: N/A
 * Importance: It was the ninth [[HIV Protease]] inhibitor approved by the FDA for treatment of HIV. It is a very potent inhibitor, and is often recommended for patients who have become resistant to other treatments, but also has a relatively harsh side-effect profile.
-* 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===
@@ Line 14: / Line 14: @@
 ===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]]
+</StructureSection>
 ===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 [[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>
+<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]]
-|-
-! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)
-! 4.4
-! ~3
-! 1.5
-! 3.7
-! .98
-! 1.5-4
-! 2
-! .5
-! 2-4
-! 3.1
-|-
-! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml)
-! 13120
-! 14600
-! 8100
-! 2297
-! 4901
-! 4820
-! 11.9
-! 2730
-! ~4393
-! 4701
-|-
-! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
-! --
-! --
-! 65
-! 4
-! --
-! --
-! --
-! --
-! 68
-! 20-80
-|-
-! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
-! 99
-! >99
-! 61
-! 98
-! 90
-! 90
-! 99
-! 95
-! 86
-! 98
-|-
-! [[Pharmaceutical_Drugs#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
-|-
-! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
-! 128100
-! 46500
-! 20900
-! 13467
-! 11999
-! 35000
-! 117600
-! 4746
-! ~26045
-! 31906
-|-
-! [[Pharmaceutical_Drugs#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===

Tipranavir: Difference between revisions

Latest revision as of 12:46, 11 January 2024

Better Known as: Aptivus

Mechanism of Action

Drug Resistance

Pharmacokinetics

References

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