QuickView for Tipranavir (compound)

Summary
General Info

PubChem

PubChem Compound 133089

Name:	tipranavir
PubChem Compound ID:	133089
Molecular formula:	C₃₁H₃₃F₃N₂O₅S
Molecular weight:	602.665 g/mol
Synonyms:	Tipranavir isomer; 2-Pyridinesulfonamide, N-(3-((1S)-1-((6R)-5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3-yl)propyl)phenyl)-5-(trifluoromethyl)-; 2-Pyridinesulfonamide, N-(3-(1-(5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3-yl)propyl)phenyl)-5-(trifluoromethyl)-, (R-(R.S))-; 2-Pyridinesulfonamide, N-[3-[(1S)-1-[(6R)-5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-; 174590-27-3; U-141166; AIDS-007998; (R-(R,S))-N-(3-(1-(5,6-Dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3-yl)propyl)phenyl)-5-(trifluoromethyl)-2-pyridinesulfonamide; Tipranavir analog 17; AIDS007998

DrugBank

Identification

Name:	tipranavir
Name (isomeric):	DB00932
Drug Type:	small molecule
Synonyms:	TPV
Brand:	Aptivus, Aptivus (Boehringer Ingelheim)
Category:	HIV Protease Inhibitors, Anti-HIV Agents
CAS number:	174484-41-4

Pharmacology

Indication:	For combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors.
Pharmacology:	Tipranavir is a non-peptidic protease inhibitor (PI) of HIV. Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the... show more » Tipranavir is a non-peptidic protease inhibitor (PI) of HIV. Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. show less «
Mechanism of Action:	Tipranavir (TPV) is a non-peptidic HIV-1 protease inhibitor that inhibits the processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions. Two mechanisms are suggested in regards to the potency of tipranavir: 1. Tipravanir may bind to the active site of the protease enzyme with fewer hyd... show more » Tipranavir (TPV) is a non-peptidic HIV-1 protease inhibitor that inhibits the processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions. Two mechanisms are suggested in regards to the potency of tipranavir: 1. Tipravanir may bind to the active site of the protease enzyme with fewer hydrogen bonds than peptidic protease inhibitors, which results in increased flexibility, allowing it to fit into the active site of the enzyme in viruses that have become resistance to other protease inhibitors. This also enables tipranavir to adjust to amino acid substitutions at the active site. 2. Tipranavir's strong hydrogen bonding interaction with the amide backbone of the protease active site Asp30 may lead to its activity against resistant viruses. show less «
Absorption:	Absorption is limited, although no absolute quantification of absorption is available.
Protein binding:	Extensive (> 99.9%), to both human serum albumin and α-1-acid glycoprotein.
Biotransformation:	Hepatic. In vitro metabolism studies with human liver microsomes indicated that CYP 3A4 is the predominant CYP enzyme involved in tipranavir metabolism.
Half Life:	5-6 hours
Toxicity:	Oral LD₅₀ in rat is over 5,000 mg/kg. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.
Affected organisms:	Human Immunodeficiency Virus

Interactions

Drug interaction:

Fosamprenavir	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Fosamprenavir. Consider alternate therapy.
Fluconazole	Fluconazole may increase the serum concentration of Tipranavir. Dose adjustments are not required.
Midazolam	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Midazolam. Concomitant therapy is contraindicated.
Clorazepate	Tipranavir may decrease the metabolism and clearance of Clorazepate. Consider alternate therapy or monitor for Clorazepate toxic effects if Tipranavir is initiated or dose increased.
Mestranol	Mestranol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Mestranol. Use an alternate form of contraception or monitor for estrogen deficiency if Mestranol is used for hormone replacement therapy.

Fosamprenavir	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Fosamprenavir. Consider alternate therapy.
Fluconazole	Fluconazole may increase the serum concentration of Tipranavir. Dose adjustments are not required.
Midazolam	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Midazolam. Concomitant therapy is contraindicated.
Clorazepate	Tipranavir may decrease the metabolism and clearance of Clorazepate. Consider alternate therapy or monitor for Clorazepate toxic effects if Tipranavir is initiated or dose increased.
Mestranol	Mestranol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Mestranol. Use an alternate form of contraception or monitor for estrogen deficiency if Mestranol is used for hormone replacement therapy.
Tadalafil	Tipranavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Desipramine	Tipranavir, co-administered with Ritonavir, may increase the concentration of Desipramine. Monitor Desipramine concentration and efficacy/toxicity and adjust dose as required.
Lopinavir	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Lopinavir. Consider alternate therapy.
Nifedipine	Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Nifedipine. Monitor for changes in Nifedipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
Sodium bicarbonate	Sodium bicarbonate may decrease the absorption of Tipranavir. Separate administration of the agents and monitor for decreased efficacy of Tipranavir.
Bromazepam	Tipranavir may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if tipranavir is initiated, discontinued or dose changed.
Dabigatran etexilate	P-Glycoprotein inducers such as tipranavir may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
Ergonovine	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Ergonovine. Concomitant therapy is contraindicated.
Phenobarbital	Phenobarbial decreases the concentration of Tipranavir. Monitor for decreased Tipranavir efficacy.
Astemizole	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Astemizole. Concomitant therapy is contraindicated.
Atorvastatin	Tipranavir, co-administered with Ritonavir, increases the adverse/toxic effects of Atorvastatin. Concomitant therapy should be avoided.
Flurazepam	Tipranavir may decrease the metabolism and clearance of Flurazepam. Consider alternate therapy or monitor for Flurazepam toxic effects if Tipranavir is initiated or dose increased.
Pimozide	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Pimozide. Concomitant therapy is contraindicated.
Pravastatin	Tipranavir may increase the plasma concentration of Pravastatin. Consider alternate therapy.
Bromocriptine	Tipranavir may increase the plasma concentration of Bromocriptine. Concomitant therapy should be avoided.
Ergoloid mesylate	Tipranavir may increase the plasma concentration of Ergoloid mesylates. Concomitant therapy should be avoided.
Delavirdine	Concomitant use may result in increased Tipranavir and decreased Delavirdine concentrations. Monitor for altered therapeutic and adverse effects of both agents if either agent is initiated, discontinued or dose changed.
Bepridil	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Bepridil. Concomitant therapy is contraindicated.
Meperidine	Tipranavir may increase the adverse/toxic effects of Meperidine. Consider alternate therapy or monitor for Meperidine toxicity during concomitant use.
Vardenafil	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Vardenafil. Concomitant therapy is contraindicated.
Methadone	Tipranavir, co-administered with Ritonavir, decreases the Methadone concentration. Monitor for symptoms of opiate withdrawal.
Efavirenz	Efavirenz may alter the serum concentration Tipranavir. Monitor for changes in Tipranavir therapeutic and adverse effects if Efavirenz is initiated, discontinued or dose changed.
Saquinavir	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Saquinavir. Consider alternate therapy.
Sertraline	Tipranavir increases the concentration of Sertraline. The Sertraline dose may require an adjustment.
Temsirolimus	Tipranavir may affect the efficacy/toxicity of Temsirolimus.
Rifabutin	Tipranavir increases the concentration of Rifabutin. Adjust Rifabutin dose and monitor for adverse/toxic effects.
Felodipine	Tipranavir, co-administered with Ritonavir, may alter the concentration of Felopidine. Monitor for efficacy and adverse/toxic effects of Felopidine.
Pergolide	Tipranavir may increase the plasma concentration of Pergolide. Concomitant therapy should be avoided.
Voriconazole	Voriconazole may increase the serum concentration of tipranavir by decreasing its metabolism. Tipranavir may increase the serum concentration of voriconazole. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Atazanavir	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Atazanavir. Consider alternate therapy.
Prazepam	Tipranavir may decrease the metabolism and clearance of Prazepam. Consider alternate therapy or monitor for Prazepam toxic effects if Tipranavir is initiated or dose increased.
Quazepam	Tipranavir may decrease the metabolism and clearance of Quazepam. Consider alternate therapy or monitor for Quazepam toxic effects if Tipranavir is initiated or dose increased.
Etravirine	Tipranavir, co-administered with Ritonavir, may decrease the effect of Etravirene by decreasing Etravirene serum concentration. Concomitant therapy should be avoided.
Disulfiram	Disulfiram may cause Tipranavir (Aptivus brand) toxicity by inhibiting alcohol metabolism. Aptivus capsules contain alcohol.
Theophylline	Tipranavir, co-administered with Ritonavir, may decrease the concentration of Theophylline.
Trazodone	The protease inhibitor, Tipranavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Tipranavir is initiated, discontinued or dose changed.
Diethylstilbestrol	Diethylstilbestrol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Diethylstilbestrol. Monitor estrogen levels during concomitant therapy.
Rifapentine	Concomitant therapy may cause decreased Tipranavir and increased Rifapentine plasma concentrations.
Estazolam	Tipranavir may decrease the metabolism and clearance of Estazolam. Consider alternate therapy or monitor for Estazolam toxic effects if Tipranavir is initiated or dose increased.
Nimodipine	Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Nimodipine. Monitor for changes in Nimodipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
Ethinyl Estradiol	Tipranavir, co-administered with Ritonavir, decreases Ethinyl estradiol concentrations. Ethinyl estradiol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Use an alternate form of contraception or monitor for estrogen deficiency if Ethinyl estradiol is used for hormone replacement therapy.
Tacrolimus	Tipranavir may decrease the metabolism and clearance of Tacrolimus. Dose adjustments may be required. Monitor for Tacrolimus efficacy and toxicity during concomitant therapy.
Amlodipine	Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Amlopidine. Monitor for changes in Amlopidine therapeutic and toxic effects if Tipranavir is initiated, discontinued or dose changed.
Fluticasone Propionate	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Fluticasone propionate. Concomitant therapy should be avoided if possible.
Rifampin	Rifampin may decrease the plasma concentration of Tipranavir. Concomitant use is not recommended.
Dihydroergotamine	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Dihydroergotamine. Concomitant therapy is contraindicated.
Sildenafil	Tipranavir, co-administered with Ritonavir, may increase the concentration of Sildenafil. Alternate therapy should be considered.
Diltiazem	Tipranavir, co-administered with Ritonavir, may alter the concentration of Diltiazem. Monitor for efficacy and adverse/toxic effects of Diltiazem.
Clarithromycin	The concentrations of Tipranavir and Clarithromycin increase during concomitant therapy. Dose adjustments are required for patients with renal impairment.
Chlordiazepoxide	Tipranavir may decrease the metabolism and clearance of Chlordiazepoxide. Consider alternate therapy or monitor for Alprazolam toxic effects if Tipranavir is initiated or dose increased.
Abacavir	The serum concentration of Abacavir may be decreased by protease inhibitors such as Tipranavir. The antiviral response should be closely monitored.
Didanosine	Tipranavir may decrease the concentration of Didanosine.
Estradiol	Estradiol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Estradiol. Use an alternate form of contraception or monitor for estrogen deficiency if Estradiol is used for hormone replacement therapy.
Itraconazole	Tipranavir may increase the serum concentration of Itraconazole.
Nevirapine	Nevirapine, a CYP3A4 inducer, may decrease the serum concentration of Tipranavir, a CYP3A4 substrate. Monitor for changesin Tipranavir effect if Nevirapine is initiated, discontinued or dose changed.
Triazolam	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Triazolam. Concomitant therapy is contraindicated.
St. John's Wort	St. John's Wort may decrease the concentration and efficacy of Tipranavir. Concomitant therapy should be avoided.
Fusidic Acid	Concomitant therapy of Tipranavir with Fusidic acid may result in increased serum concentrations of both agents. Consider alternate therapy or monitor for increased serum concentrations and toxocity of both agents.
Paroxetine	Tipranavir increases the concentration of Paroxetine. The Paroxetine dose may require an adjustment.
Rosuvastatin	Concomitant therapy of Rosuvastatin and Tipranavir/Ritonavir may increase Rosuvastatin and Tipranavir concentrations. Consider alternate therapy.
Ergotamine	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Ergotamine. Concomitant therapy is contraindicated.
Propafenone	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Propafenone. Concomitant therapy is contraindicated.
Diazepam	Tipranavir may decrease the metabolism and clearance of Diazepam. Consider alternate therapy or monitor for Diazepam toxic effects if Tipranavir is initiated or dose increased.
Nisoldipine	Tipranavir, co-administered with Ritonavir, may alter the concentration of Nisoldipine. Monitor for efficacy and adverse/toxic effects of Nisoldipine.
Valproic Acid	Tipranavir decreases the concentration of Valproic acid. Monitor Valproid acid efficacy.
Quinidine	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Quinidine. Concomitant therapy is contraindicated.
Ketoconazole	Tipranavir may increase the serum concentration of Ketoconazole.
Clobazam	Tipranavir may decrease the metabolism and clearance of Clobazam. Consider alternate therapy or monitor for Clobazam toxic effects if Tipranavir is initiated or dose increased.
Nicardipine	Tipranavir, co-administered with Ritonavir, may alter the concentration of Nicardipine. Monitor for efficacy and adverse/toxic effects of Nicardipine.
Esomeprazole	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Esomeprazole. Consider alternate therapy or increase the dose of Esomeprazole based on the therapeutic response.
Fluoxetine	Tipranavir increases the concentration of Fluoxetine. The Fluoxetine dose may require an adjustment.
Methylergonovine	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Methylergonovine. Concomitant therapy is contraindicated.
Verapamil	Tipranavir, co-administered with Ritonavir, may alter the concentration of Verapamil. Monitor for efficacy and adverse/toxic effects of Verapamil.
Lovastatin	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Lovastatin. Concomitant therapy is contraindicated.
Amiodarone	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Amiodarone. Concomitant therapy is contraindicated.
Budesonide	Tipranavir may increase the plasma concentration of Budesonide. Monitor for toxic Budesonide effects during concomitant administration.
Carbamazepine	Concomitant use may result in decreased Tipranavir and increased Carbamazepine concentrations.
Simvastatin	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Simvastatin. Concomitant therapy is contraindicated.
Terfenadine	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Terfenadine. Concomitant therapy is contraindicated.
Ranolazine	Increased levels of ranolazine - risk of toxicity
Nitrendipine	Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Nitrendipine. Monitor for changes in Nitrendipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
Phenytoin	Phenytoin decreases the concentration of Tipranavir. Monitor for decreased Tipranavir efficacy.
Alprazolam	Tipranavir may decrease the metabolism and clearance of Alprazolam. Consider alternate therapy or monitor for Alprazolam toxic effects if Tipranavir is initiated or dose increased.
Clonazepam	Tipranavir may decrease the metabolism and clearance of Clonazepam. Consider alternate therapy or monitor for Clonazepam toxic effects if Tipranavir is initiated or dose increased.
Zidovudine	Tipranavir decreases the concentration of Zidovudine.
Cisapride	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Cisapride. Concomitant therapy is contraindicated.
Flecainide	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Flecainide. Concomitant therapy is contraindicated.
Sirolimus	Tipranavir may affect the efficacy/toxicity of Sirolimus.
Omeprazole	Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Omeprazole. Consider alternate therapy or increase the dose of Omeprazole based on the therapeutic response.
Estrone	Estropipate may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Estropipate. Monitor for estrogen deficiency during concomitant therapy.
Cyclosporine	Tipranavir may affect the efficacy/toxicity of Cyclosporine.
Posaconazole	Tipranavir may increase the serum concentration of Posaconazole. Posaconazole may increase the serum concentration of Tipranavir.
Isradipine	Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Isradipine. Monitor for changes in Isradipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
Conjugated Estrogens	Conjugated estrogens may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Conjugated estrogens. Monitor for estrogen deficiency during concomitant therapy.

Targets

UniProt ID:

Gene:

Actions:

inhibitor

References:

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View Article

Muzammil S, Armstrong AA, Kang LW, Jakalian A, Bonneau PR, Schmelmer V, Amzel LM, Freire E: Unique thermodynamic response of tipranavir to human immunodeficiency virus type 1 protease drug resistance mutations. J Virol. 2007 May;81(10):5144-54. Epub 2007 Mar 14.
View Article

Hsieh SM, Chang SY, Hung CC, Sheng WH, Chen MY, Chang SC: Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure. BMC Infect Dis. 2009 Sep 14;9:154.
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Temesgen Z, Feinberg J: Tipranavir: a new option for the treatment of drug-resistant HIV infection. Clin Infect Dis. 2007 Sep 15;45(6):761-9. Epub 2007 Aug 7.
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Luna B, Townsend MU: Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance. Clin Ther. 2007 Nov;29(11):2309-18.
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Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
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Enzymes

Cytochrome P450 3A4

Cytochrome P450 2D6

Cytochrome P450 2C19