Tìm theo
Itraconazole
Các tên gọi khác (6 ) :
  • Itraconazol
  • Itraconazole
  • Itraconazolum
  • Itrizole (tn)
  • Oriconazole
  • Sporanox (tn)
Thuốc trị ký sinh trùng, chống nhiễm khuẩn
Thuốc Gốc
Small Molecule
CAS: 84625-61-6
ATC: J02AC02
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C35H38Cl2N8O4
PTK: 705.633
One of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C35H38Cl2N8O4
Phân tử khối
705.633
Monoisotopic mass
704.239307158
InChI
InChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1
InChI Key
InChIKey=VHVPQPYKVGDNFY-ZPGVKDDISA-N
IUPAC Name
1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
Traditional IUPAC Name
itraconazole
SMILES
CCC(C)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OC[C@H]2CO[C@@](CN3C=NC=N3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1
Độ tan chảy
166.2 °C
Độ hòa tan
Insoluble
logP
5.66
logS
-4.9
pKa (Strongest Basic)
3.92
PSA
100.79 Å2
Refractivity
200.4 m3·mol-1
Polarizability
74.7 Å3
Rotatable Bond Count
11
H Bond Acceptor Count
9
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
7
Bioavailability
0
MDDR-Like Rule
true
pKa
3.70
Dược Lực Học : Itraconazole is an imidazole/triazole type antifungal agent. Itraconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.
Cơ Chế Tác Dụng : One of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis. [PubChem] Itraconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
Dược Động Học :
▧ Absorption :
The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.
▧ Volume of Distribution :
* 796 ± 185 L
▧ Protein binding :
99.8%
▧ Metabolism :
Itraconazole is extensively metabolized by the liver into a large number of metabolites, including hydroxyitraconazole, the major metabolite. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N-dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission.
▧ Route of Elimination :
Itraconazole is metabolized predominately by the cytochrome P450 3A4 isoenzyme system (CYP3A4) in the liver, resulting in the formation of several metabolites, including hydroxyitraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a dose.
▧ Half Life :
21 hours
▧ Clearance :
* 381 +/- 95 mL/minute [IV administration]
Độc Tính : No significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.
Chỉ Định : For the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.
Tương Tác Thuốc :
  • Abiraterone Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
  • Acenocoumarol Itraconazole may increase the anticoagulant effect of acenocoumarol.
  • Alfentanil Itraconazole may increase the effect and toxicity of alfentanil.
  • Alfuzosin The antifungal increases the effect of alfuzosin
  • Aliskiren Avoid combination due to increased serum concentration of aliskiren.
  • Almotriptan This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
  • Alprazolam Itraconazole may increase the effect of the benzodiazepine, alprazolam.
  • Aluminium Aluminum-containing antacids may decrease the effect of itraconazole.
  • Anisindione Itraconazole may increase the anticoagulant effect of anisindione.
  • Apixaban Avoid combination. Otherwise, itraconazole will likely increase apixaban serum concentration.
  • Aprepitant This CYP3A4 inhibitor, itraconazole, may increase the effect and toxicity of aprepitant.
  • Aripiprazole Itraconazole may increase the effect of aripiprazole.
  • Astemizole Increased risk of cardiotoxicity and arrhythmias
  • Atorvastatin Increased risk of myopathy/rhabdomyolysis
  • Bosentan Itraconazole may increase the effect and toxicity of bosentan.
  • Bromazepam Itraconazole may increase the serum concentration of bromazepam by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if itraconazole is initiated, discontinued or dose changed.
  • Budesonide Itraconazole may increase levels/effect of budesonide.
  • Busulfan Itraconazole reduced busulfan clearance by up to 25% in patients receiving itraconazole compared to those that did not receive it. Concomitant therapy may lead to toxic plasma levels of busulfan.
  • Cabazitaxel Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
  • Calcium Calcium-containing antacids may decrease the effect of itraconazole.
  • Calcium carbonate The antacid, calcium carbonate, may decrease the effect of itraconazole by decreasing its absorption.
  • Carbamazepine Itraconazole may increase the effect of carbamazepine.
  • Celiprolol Itaconazole increases levels/effect of celiprolol
  • Cerivastatin Increased risk of myopathy/rhabdomyolysis
  • Chlordiazepoxide Itraconazole may increase the effect of the benzodiazepine, chlordiazepoxide.
  • Ciclesonide Increased effects/toxicity of ciclesonide
  • Cilostazol Itraconazole may increase the effect of cilostazol.
  • Cimetidine The H2-receptor antagonist, cimetidine, may decrease the absorption of itraconazole.
  • Cinacalcet Itraconazole may increase the effect and toxicity of cinacalcet.
  • Cisapride Increased risk of cardiotoxicity and arrhythmias
  • Clarithromycin The macrolide, clarithromycin, may increase the effect and toxicity of itraconazole.
  • Clonazepam Itraconazole may increase the effect of the benzodiazepine, clonazepam.
  • Clorazepate Itraconazole may increase the effect of the benzodiazepine, clorazepate.
  • Conivaptan Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
  • Cyclosporine Itraconazole may increase the effect of cyclosporine.
  • Dantrolene Itraconazole 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 itraconazole is initiated, discontinued or dose changed.
  • Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Diazepam Itraconazole may increase the effect of the benzodiazepine, diazepam.
  • Dicoumarol Itraconazole may increase the anticoagulant effect of dicumarol.
  • Digoxin Itraconazole increases the effect of digoxin
  • Dihydroergotamine Possible ergotism and severe ischemia with this combination
  • Dofetilide This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
  • Dronedarone Itraconazole is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
  • Eletriptan This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
  • Eplerenone Itraconazole may increase the effect and toxicity of eplerenone.
  • Ergotamine Possible ergotism and severe ischemia with this combination
  • Erlotinib Itraconazole may decrease the metabolism of erlotinib. Monitor for changes in the therapeutic and adverse effects of erlotinib if itraconazole is initiated, discontinued or dose changed.
  • Erythromycin The macrolide, erythromycin, may increase the effect and toxicity of itraconazole.
  • Esomeprazole The proton pump inhibitor, esomeprazole, may decrease the absorption of itraconazole.
  • Estazolam Itraconazole may increase the effect of the benzodiazepine, estazolam.
  • Ethotoin Phenytoin decreases the effect of itraconazole
  • Everolimus Itraconazole may increase everolimus levels/toxicity.
  • Famotidine The H2-receptor antagonist, famotidine, may decrease the absorption of itraconazole.
  • Felodipine Itraconazole may increase the therapeutic and adverse effects of felodipine.
  • Fentanyl Itraconazole may increase levels/toxicity of fentanyl.
  • Flurazepam Itraconazole may increase the effect of the benzodiazepine, flurazepam.
  • Fosphenytoin Phenytoin decreases the effect of itraconazole
  • Gefitinib Itraconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of gefitinib. Monitor for changes in the therapeutic and adverse effects of gefitinib if itraconazole is initiated, discontinued or dose changed.
  • Halazepam Itraconazole may increase the effect of the benzodiazepine, halazepam.
  • Haloperidol Itraconazole may increase the effect and toxicity of haloperidol.
  • Imatinib Itraconazole may increase the levels of imatinib.
  • Ivacaftor Strong CYP3A4 inhibitors may increase levels of ivacaftor. Monitor concomitant therapy closely.
  • Josamycin The macrolide, josamycin, may increase the effect and toxicity of itraconazole.
  • Lansoprazole The proton pump inhibitor, lansoprazole, may decrease the absorption of itraconazole.
  • Levomethadyl Acetate Itraconazole increases the effect/toxicity of levomethadyl
  • Lovastatin Increased risk of myopathy/rhabdomyolysis
  • Lurasidone Concomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
  • Magnesium oxide The antacid, magnesium oxide, may decrease the effect of itraconazole by decreasing its absorption.
  • Mephenytoin Phenytoin decreases the effect of itraconazole
  • Mestranol This anti-infectious agent could decrease the effect of the oral contraceptive
  • Methylprednisolone The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, methylprednisolone.
  • Midazolam Itraconazole may increase the effect of the benzodiazepine, midazolam.
  • Nizatidine The H2-receptor antagonist, nizatidine, may decrease the absorption of itraconazole.
  • Omeprazole The proton pump inhibitor, omeprazole, may decrease the absorption of itraconazole.
  • Pantoprazole The proton pump inhibitor, pantoprazole, may decrease the absorption of itraconazole.
  • Pazopanib Affects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib. Consider alternate therapy.
  • Phenobarbital The barbiturate, phenobarbital, decreases the effect of itraconazole.
  • Phenytoin Phenytoin decreases the effect of itraconazole
  • Pimozide Increased risk of cardiotoxicity and arrhythmias
  • Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
  • Prednisolone The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, prednisolone.
  • Prednisone The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, prednisone.
  • Quazepam Itraconazole may increase the effect of the benzodiazepine, quazepam.
  • Quinidine Itraconazole may increase the effect and toxicity of quinidine.
  • Quinidine barbiturate Itraconazole may increase the effect and toxicity of quinidine barbiturate.
  • Rabeprazole The proton pump inhibitor, rabeprazole, may decrease the absorption of itraconazole.
  • Ranitidine The H2-receptor antagonist, ranitidine, may decrease the absorption of itraconazole.
  • Ranolazine Increased levels of ranolazine - risk of toxicity
  • Regorafenib Strong CYP3A4 inhibitors may increase levels of regorafenib.
  • Rifabutin Rifabutin decreases the effect of itraconazole
  • Rifampicin Rifampin may decrease the effect of itraconazole.
  • Risperidone Increases the level of risperidone
  • Ritonavir Itraconazole may increase the effect and toxicity of ritonavir.
  • Rivaroxaban Use of rivaroxaban with agents that are strong inhibitors of both CYP3A4 and P-glycoproteins are contraindicated.
  • Ruxolitinib Strong CYP3A4 inhibitors may increase levels of ruxolitinib. Consider alternate therapy.
  • Sildenafil Itraconazole may increase the effect and toxicity of sildenafil.
  • Silodosin Strong CYP3A4 inhibitors may increase levels of silodosin. Concomitant administration is contraindicated.
  • Simvastatin Increased risk of myopathy/rhabdomyolysis
  • Sirolimus Itraconazole may increase the effect and toxicity of sirolimus.
  • Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Sucralfate Sucralfate may decrease the absorption of itraconazole.
  • Sunitinib Possible increase in sunitinib levels
  • Tacrolimus The antifungal, Itraconazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Itraconazole therapy is initiated, discontinued or altered.
  • Tadalafil Itraconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
  • Tamoxifen Itraconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
  • Tamsulosin Itraconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Itraconazole is initiated, discontinued, or dose changed.
  • Telithromycin Itraconazole may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
  • Temsirolimus Itraconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
  • Teniposide The strong CYP3A4 inhibitor, Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
  • Terfenadine Increased risk of cardiotoxicity and arrhythmias
  • Tiagabine The strong CYP3A4 inhibitor, Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
  • Tipranavir Tipranavir may increase the serum concentration of Itraconazole.
  • Tolterodine Itraconazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Tolvaptan Itraconazole is a strong inhibitor of CYP3A4 and will increase serum concentrations of tolvaptan.
  • Topotecan The p-glycoprotein inhibitor, Itraconazole, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Tramadol Itraconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
  • Trazodone The CYP3A4 inhibitor, Itraconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Itraconazole is initiated, discontinued or dose changed.
  • Triazolam Itraconazole may increase the effect of the benzodiazepine, triazolam.
  • Trimipramine The strong CYP3A4 inhibitor, Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
  • Ulipristal Concomitant therapy with strong CYP3A4 inhibitors may increase plasma concentrations of ulipristal. Avoid combination therapy.
  • Vardenafil Itraconazole, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
  • Vemurafenib Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Venlafaxine Itraconaole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Itraconazole is initiated, discontinued, or dose changed.
  • Verapamil Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
  • Vinblastine Itraconazole, 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 Itraconazole is initiated, discontinued or dose changed.
  • Vincristine Itraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Itraconazole is initiated, discontinued or dose changed.
  • Vinorelbine Itraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Itraconazole is initiated, discontinued or dose changed.
  • Warfarin Itraconazole may increase the anticoagulant effect of warfarin by decreasing its metabolism.
  • Zolpidem Itraconazole, 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 itraconazole is initiated, discontinued or dose changed.
  • Zonisamide Itraconazole, 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 itraconazole is initiated, discontinued or dose changed.
  • Zopiclone Itraconazole, 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 itraconzole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Capsule - Oral
Liquid - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Itrizole
  • Công ty :
    Sản phẩm biệt dược : Onmel
  • Công ty :
    Sản phẩm biệt dược : Oriconazole
  • Công ty :
    Sản phẩm biệt dược : Sporal
  • Công ty :
    Sản phẩm biệt dược : Sporanox
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01167
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=55283
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505954
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00350
ChemSpider
http://www.chemspider.com/Chemical-Structure.49927.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50458-295-15
PharmGKB
http://www.pharmgkb.org/drug/PA450132
Wikipedia
http://en.wikipedia.org/wiki/Itraconazole
RxList
http://www.rxlist.com/cgi/generic/itraconazole.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/spo1411.shtml
Drugs.com
http://www.drugs.com/cdi/itraconazole.html
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