| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
others
Voriconazole itself inhibits fungal CYP51 (14alpha‑demethylase), thereby blocking ergosterol synthesis and compromising fungal cell membrane integrity. Voriconazole N‑oxide itself lacks significant antifungal activity but retains the ability to interact with and inhibit human CYP enzymes, particularly CYP2C19 and CYP3A4, thereby contributing to the non‑linear pharmacokinetics of the parent drug. |
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| ln Vitro |
Voriconazole N‑oxide does not exhibit direct antifungal activity in standard susceptibility tests against Candida or Aspergillus species. However, in human hepatocytes and liver microsomes, it acts as a metabolite‑mediated CYP inhibitor, reducing the metabolic clearance of voriconazole and other CYP substrates in a concentration‑dependent manner.
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| ln Vivo |
In rats and humans, voriconazole N‑oxide is the predominant metabolite circulating in plasma, but it does not contribute to the overall antifungal effect. Its accumulation, especially in patients with CYP2C19 poor metabolizer status, correlates with increased exposure to voriconazole and a higher risk of adverse events, likely through feedback inhibition of CYP enzymes.
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| Enzyme Assay |
In vitro inhibition assays use human liver microsomes and probe substrates such as omeprazole (for CYP2C19) or midazolam (for CYP3A4). Incubations include voriconazole N‑oxide (0.1‑100 uM) plus NADPH. After termination with acetonitrile, metabolite formation is quantified by LC‑MS/MS. IC50 values are calculated by comparing metabolite production to control incubations.
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| Cell Assay |
Human hepatocytes are cultured in suspension or monolayer format and treated with voriconazole (0.1‑50 uM). After incubation for 1‑4 hours, the disappearance of voriconazole and the formation of voriconazole N‑oxide are measured by LC‑MS/MS. Such assays can include the addition of exogenous voriconazole N‑oxide to study its own inhibitory effects on its formation (auto‑inhibition).
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| Animal Protocol |
Animals (rats or dogs) are dosed intravenously or orally with voriconazole. Serial blood samples are collected, and plasma concentrations of both voriconazole and voriconazole N‑oxide are measured by validated LC‑MS/MS assays. Non‑compartmental or compartmental modeling is then performed to estimate formation and elimination clearances and to assess the role of metabolite‑mediated inhibition.
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| ADME/Pharmacokinetics |
Voriconazole N‑oxide has a long elimination half‑life (often >24 hours) and tends to accumulate in humans. Its formation is dependent on CYP2C19 genotype, resulting in large inter‑individual variability. The metabolite is highly protein‑bound and is mainly excreted in the urine as further conjugates or oxidation products.
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| Toxicity/Toxicokinetics |
Voriconazole N‑oxide does not exert direct organ toxicity, but its accumulation is associated with a higher incidence of voriconazole‑related adverse effects, including hepatotoxicity, visual disturbances, and neurotoxicity, because it contributes to the non‑linear pharmacokinetics and elevated parent drug exposure.
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| References | |
| Additional Infomation |
Although voriconazole N‑oxide lacks antifungal activity, it is a critical player in voriconazole pharmacokinetics. The hydrochloride salt form is used in research to improve aqueous solubility. Understanding the role of this metabolite has been key to developing physiologically based pharmacokinetic models for voriconazole and for optimizing dosing regimens, especially in patients with CYP2C19 polymorphisms.
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| Molecular Formula |
C16H15CLF3N5O2
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|---|---|
| Molecular Weight |
401.77
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| Appearance |
White to off-white solid powder
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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)
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| Solubility (In Vitro) |
DMSO :~125 mg/mL (~311.12 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4890 mL | 12.4449 mL | 24.8899 mL | |
| 5 mM | 0.4978 mL | 2.4890 mL | 4.9780 mL | |
| 10 mM | 0.2489 mL | 1.2445 mL | 2.4890 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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