| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
Hydroxyitraconazole targets fungal cytochrome P450-dependent 14α-demethylase (CYP51), an enzyme essential for ergosterol biosynthesis in fungal cell membranes. By inhibiting ergosterol synthesis, it disrupts fungal cell membrane integrity and function, leading to growth inhibition and cell death.
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| ln Vitro |
The active metabolite of itraconazole (ITZ) is hydroxyitraconazole (itraconazole metabolite hydroxyitraconazole; R-63373). Despite reports of in vitro antifungal effectiveness, hydroxyitraconazole's human pharmacokinetic research has not been as extensive as that of ITZ. Because they include a triazole ring, ITZ and hydroxyitraconazole block CYP3A. Reusable medications have a half-life that is 26–60% longer than that of single-use medications [1].
In vitro, hydroxyitraconazole exhibits broad-spectrum antifungal activity comparable to that of itraconazole. It is effective against various fungal species including Candida spp., Aspergillus spp., and dermatophytes. Antifungal susceptibility testing is performed using CLSI or EUCAST broth microdilution methods. MIC values are typically similar to those of the parent compound. |
| ln Vivo |
The method by which hydroxyitraconazole has been absorbed is most likely what causes the concentration of hydroxyitraconazole, which is only marginally influenced by the dose of ITZ. ITZ and hydroxyitraconazole pharmacokinetics may be affected by serum albumin and GFR. It's crucial to take into account both the intravenous concentration of ITZ and the concentration of hydroxyitraconazole when talking about antifungal activity. However, the pharmacokinetics of hydroxyitraconazole are identical to those of ITZ in immunocompromised individuals receiving the intravenous solution of the drug. Given the strong relationship between the intravenous concentrations of ITZ and hydroxyitraconazole, the clinically measured Marathon concentration ought to be enough [1].
In vivo, hydroxyitraconazole contributes significantly to the overall antifungal effects of itraconazole therapy. It has a prolonged half-life and high plasma concentration, playing an essential role in treating systemic fungal infections. It is widely used clinically in immunocompromised patients. |
| Enzyme Assay |
In vitro antifungal susceptibility testing follows CLSI (M27, M38) or EUCAST broth microdilution methodologies. Serial two-fold dilutions of hydroxyitraconazole are prepared in RPMI 1640 medium. Fungal inocula are standardized spectrophotometrically. MICs are determined after 24-48 h incubation as the lowest concentration inhibiting visible fungal growth.
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| Cell Assay |
Fungal cells (e.g., Candida albicans, Aspergillus fumigatus) are cultured in RPMI 1640 with MOPS buffer at 35°C. Cells are seeded in 96-well plates, treated with hydroxyitraconazole at various concentrations, and incubated for 24-48 h. Fungal growth is assessed spectrophotometrically at 530 nm or by visual inspection. IC₅₀/MIC values are determined.
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| Animal Protocol |
In vivo antifungal efficacy is evaluated in animal models of systemic fungal infection (e.g., murine candidiasis, aspergillosis). Immunocompromised mice are infected intravenously or intranasally with fungal pathogens, then treated with hydroxyitraconazole orally or intraperitoneally. Survival rates, tissue fungal burden, and histopathology are assessed.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Hydroxyitraconazole is a known human metabolite of itraconazole. Hydroxyitraconazole has a prolonged half-life and reaches high plasma concentrations, often exceeding those of the parent compound itraconazole. It is highly protein-bound (>99%). It undergoes enterohepatic circulation. Excretion is primarily via the hepatobiliary route, with minimal renal excretion. Its pharmacokinetic profile contributes significantly to the therapeutic efficacy of itraconazole therapy. |
| Toxicity/Toxicokinetics |
Hydroxyitraconazole shares the toxicity profile of itraconazole. Adverse effects may include hepatotoxicity (elevated liver enzymes), gastrointestinal disturbances, and drug-drug interactions due to CYP3A4 inhibition. It is teratogenic in animals and contraindicated during pregnancy. Cardiac effects (QT prolongation) have been reported at high concentrations.
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| References | |
| Additional Infomation |
See also: Hydroxytraconazole (note moved to).
Hydroxyitraconazole (OH-ITZ; R-63373) is the primary circulating metabolite of itraconazole. It has in vitro antifungal activity similar to the parent drug and contributes to the overall clinical efficacy of itraconazole therapy. It is used as a reference standard in therapeutic drug monitoring of itraconazole treatment. |
| Molecular Formula |
C35H38CL2N8O5
|
|---|---|
| Molecular Weight |
721.64
|
| Exact Mass |
720.234
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| CAS # |
112559-91-8
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| Related CAS # |
Hydroxy Itraconazole-d8;(2R,4S)-Hydroxy Itraconazole-d5;1217524-77-0;Itraconazole;84625-61-6;(2R,4S)-Hydroxy Itraconazole-d8;1217516-26-1
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| PubChem CID |
108222
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| Appearance |
White to off-white solid powder
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| Density |
1.44g/cm3
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| Boiling Point |
884.7ºC at 760mmHg
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| Melting Point |
76-78ºC
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| Flash Point |
488.8ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.687
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| LogP |
4.967
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
50
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| Complexity |
1150
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ISJVOEOJQLKSJU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H38Cl2N8O5/c1-24(25(2)46)45-34(47)44(23-40-45)29-6-4-27(5-7-29)41-13-15-42(16-14-41)28-8-10-30(11-9-28)48-18-31-19-49-35(50-31,20-43-22-38-21-39-43)32-12-3-26(36)17-33(32)37/h3-12,17,21-25,31,46H,13-16,18-20H2,1-2H3
|
| Chemical Name |
4-[4-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-(3-hydroxybutan-2-yl)-1,2,4-triazol-3-one
|
| Synonyms |
R-63373; R 63373; Hydroxyitraconazole
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~83.33 mg/mL (~115.47 mM)
H2O : ~1 mg/mL (~1.39 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3857 mL | 6.9287 mL | 13.8573 mL | |
| 5 mM | 0.2771 mL | 1.3857 mL | 2.7715 mL | |
| 10 mM | 0.1386 mL | 0.6929 mL | 1.3857 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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