QuickView for darunavir (compound)

Summary
General Info

PubChem

PubChem Compound 213039

Name:	darunavir
PubChem Compound ID:	213039
Molecular formula:	C₂₇H₃₇N₃O₇S
Molecular weight:	547.665 g/mol
Synonyms:	Darunavir; TMC-114; 206361-99-1; 618109-00-5; Prezista; UIC-94017; (3R,3aS,6aR)-Hexahydrofuro(2,3-b)furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N1-isobutylsulfanilamido)propyl)carbamate; UIC 94017; AIDS-073035; TMC 114. show more » Darunavir; TMC-114; 206361-99-1; 618109-00-5; Prezista; UIC-94017; (3R,3aS,6aR)-Hexahydrofuro(2,3-b)furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N1-isobutylsulfanilamido)propyl)carbamate; UIC 94017; AIDS-073035; TMC 114; Sulfonamide isostere; (3-((4-aminobenzenesulfonyl)isobutylamino)-1-benzyl-2-hydroxypropyl)carbamic acid hexahydrofuro(2,3-b)furan-3-yl ester; (3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE; N-((1S,2R)-3-(((4-Aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-benzylpropyl)((1S,2R,5R)-4,6-dioxabicyclo(3.3.0)oct-2-yloxy)carboxamide; D03656; TMC114; AIDS073035; Darunavir [INN]; Carbamic acid, [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-, (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester; Darunavir (USAN); Darunavirum [INN-Latin] show less «

DrugBank

Identification

Name:	darunavir
Name (isomeric):	DB01264
Drug Type:	small molecule
Synonyms:	Darunavirum [INN-latin]; TMC-114; UIC-94017; TMC114; AIDS073035
Brand:	Prezista
Category:	HIV Protease Inhibitors, Antiviral Agents
CAS number:	206361-99-1

Pharmacology

Indication:	Darunavir, co-administered with ritonavir, and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.
Pharmacology:	Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006). Darunavir is used as an adjunct... show more » Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006). Darunavir is used as an adjunct therapy with low dose ritonavir, which inhibits cytochrome P450 3A (CYP3A) which increases the bioavailability and half life of darunavir. show less «
Mechanism of Action:	Darunavir is a HIV protease inhibitor which prevents HIV replication by binding to the enzyme's active site, thereby preventing the dimerization and the catalytic activity of the HIV-1 protease. Darunavir selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious ... show more » Darunavir is a HIV protease inhibitor which prevents HIV replication by binding to the enzyme's active site, thereby preventing the dimerization and the catalytic activity of the HIV-1 protease. Darunavir selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious virus particles. Structual analyses suggests that the close contact that darunavir has with the main chains of the protease active site amino acids (Asp-29 and Asp-30) is an important contributing factor to its potency and wide spectrum of activity against multi-protease inhibitor resistant HIV-1 variants. Darunavir can also adapt to the changing shape of a protease enzyme because of its molecular flexibility. Darunavir is known to bind to two distinct sites on the enzyme: the active site cavity and the surface of one of the flexible flaps in the protease dimer. show less «
Absorption:	The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.
Protein binding:	Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).
Biotransformation:	Hepatic. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.
Route of elimination:	Darunavir is primarily metabolized by CYP3A. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A. A mass balance study in healthy volunteers showed that after single dose administration of 400 mg 14C-darunavir, co-administered with 100 mg ritonavir, approximately 79.5% and 13.9% of the administered dose of 14C-darunavir was recovered in the feces and urine, respectively.
Half Life:	The terminal elimination half-life of darunavir was approximately 15 hours when combined with ritonavir.
Clearance:	32.8 L/hr [Healthy volunteers receiving intravenous administration of 400 mg of darunavir] 5.9 L/hr [Healthy volunteers receiving intravenous administrations of 400 mg of darunavir and 100 mg of ritonavir twice daily]
Affected organisms:	Human Immunodeficiency Virus

Interactions

Food interaction:

Take with food - better absorption (+30%).

Drug interaction:

Tramadol	Darunavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Saquinavir	Decreased levels of darunavir
Tacrolimus	The protease inhibitor, Darunavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Darunavir therapy is initiated, discontinued or altered.
Zopiclone	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if darunavir is initiated, discontinued or dose changed.
Tadalafil	Darunavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.

Tramadol	Darunavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Saquinavir	Decreased levels of darunavir
Tacrolimus	The protease inhibitor, Darunavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Darunavir therapy is initiated, discontinued or altered.
Zopiclone	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if darunavir is initiated, discontinued or dose changed.
Tadalafil	Darunavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamsulosin	Darunavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Darunavir is initiated, discontinued, or dose changed.
Bromazepam	Darunavir, a strong CYP3A4 inhibitor, 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 darunavir is initiated, discontinued or dose changed. Dosage adjustments may be required.
Topotecan	The p-glycoprotein inhibitor, Darunavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Lopinavir	Decreased levels of darunavir
Abacavir	The serum concentration of Abacavir may be decreased by protease inhibitors such as Darunavir. The antiviral response should be closely monitored.
Teniposide	The strong CYP3A4 inhibitor, Darunavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Darunavir is initiated, discontinued or dose changed.
Vincristine	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Darunavir is initiated, discontinued or dose changed.
Vardenafil	Darunavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Dantrolene	Darunavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if darunavir is initiated, discontinued or dose changed.
Zonisamide	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if darunavir is initiated, discontinued or dose changed.
Lovastatin	Darunavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Tolterodine	Darunavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tiagabine	The strong CYP3A4 inhibitor, Darunavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Darunavir is initiated, discontinued or dose changed.
Temsirolimus	Darunavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Lidocaine	Possible increase in lidocaine levels
Zolpidem	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if darunavir is initiated, discontinued or dose changed.
Clarithromycin	Increased levels of clarithromycin
Trimipramine	The strong CYP3A4 inhibitor, Darunavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Darunavir is initiated, discontinued or dose changed.
Tamoxifen	Darunavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
Verapamil	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Darunavir is initiated, discontinued or dose changed.
Vinorelbine	Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Darunavir is initiated, discontinued or dose changed.
Telithromycin	Co-administration may result in altered plasma concentrations of Darunavir and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
Voriconazole	Darunavir may reduce serum concentrations and efficacy of voriconazole. This combination should be avoided unless the potential benefits outweigh the risk of reduced voriconazole efficacy.
Venlafaxine	Darunavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Darunavir is initiated, discontinued, or dose changed.
Vinblastine	Darunavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Darunavir is initiated, discontinued or dose changed.
Trazodone	The protease inhibitor, Darunavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Darunavir is initiated, discontinued or dose changed.

Targets

UniProt ID:

Gene:

Actions:

inhibitor

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
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Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
View Article

Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to HIV-1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Oct 10;.
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Ghosh AK, Dawson ZL, Mitsuya H: Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. Bioorg Med Chem. 2007 Sep 14;.
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Wang YF, Tie Y, Boross PI, Tozser J, Ghosh AK, Harrison RW, Weber IT: Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. J Med Chem. 2007 Sep 6;50(18):4509-15. Epub 2007 Aug 16.
View Article

McKeage K, Perry CM, Keam SJ: Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503.
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Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66.
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Kovalevsky AY, Tie Y, Liu F, Boross PI, Wang YF, Leshchenko S, Ghosh AK, Harrison RW, Weber IT: Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. J Med Chem. 2006 Feb 23;49(4):1379-87.
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De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP: TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005 Jun;49(6):2314-21.
View Article

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
View Article

Enzymes

Cytochrome P450 3A4