Hedgehog (Hh) signaling pathway, specifically Smoothened (Smo) protein (IC50 ≈ 100 nM, determined by Smo-mediated Gli luciferase reporter gene activity in HEK293 cells) [1]
- Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) (IC50 ≈ 5 μM, measured by VEGFR2 kinase activity assay) and Phosphoinositide 3-Kinase (PI3K) (IC50 ≈ 2 μM, measured by PI3K kinase activity assay) [2]
- Oxysterol-Binding Protein (OSBP) (IC50 ≈ 2 μM, determined by OSBP-cholesterol binding assay) and Hedgehog (Hh) signaling pathway (IC50 ≈ 150 nM for Gli reporter activity in PANC-1 cells) [3]

伊曲康唑抑制 HUVEC 增殖（IC50 为 0.16 μM）[2]。在体外，伊曲康唑抑制内皮细胞周期的 G1 期[1]。

---

1. 抑制Hedgehog（Hh）通路及癌细胞增殖：在共转染Gli荧光素酶报告质粒、Smo表达质粒的HEK293细胞中，Itraconazole浓度依赖性抑制Smo介导的Gli转录活性，IC50约100 nM；200 nM时抑制率超80%。对Hh依赖性癌细胞系（如DAOY髓母细胞瘤细胞、MB031胶质母细胞瘤细胞），Itraconazole通过CCK-8法检测显示其增殖抑制IC50为50-200 nM。Western blot分析表明，100 nM Itraconazole处理DAOY细胞48小时后，Hh通路下游效应因子Gli1蛋白表达下调约60% [1]
2. 抗血管生成活性：Itraconazole抑制VEGF诱导的人脐静脉内皮细胞（HUVEC）增殖，MTT法测定IC50约3 μM。Transwell迁移实验中，10 μM Itraconazole处理24小时可减少60%的VEGF诱导HUVEC迁移；Matrigel管形成实验中，10 μM Itraconazole处理6小时可减少70%的HUVEC总管长。Western blot显示，5 μM Itraconazole可使HUVEC中VEGF诱导的VEGFR2磷酸化（p-VEGFR2）降低50%，PI3K磷酸化（p-PI3K）降低45% [2]
3. 抑制OSBP及与化疗药协同抗肿瘤：体外OSBP胆固醇转运实验中，2 μM Itraconazole抑制OSBP介导的膜间胆固醇转运达75%。与紫杉醇（化疗药）联用时，Itraconazole可增强A549肺癌细胞的增殖抑制活性：5 μM Itraconazole+10 nM紫杉醇处理72小时，增殖抑制率约85%，显著高于10 nM紫杉醇单药组（约45%）。对Hh依赖性PANC-1胰腺癌细胞，Itraconazole抑制Gli报告基因活性的IC50约150 nM，与文献[1]结果一致 [3]

在小鼠同种异体移植模型中，替那唑治疗（75-100 mg/kg；口服灌胃；每天两次；持续 18 天；雌性远交无胸腺裸鼠）抑制髓母细胞瘤的生长和 Hh 通路活性[1]。

---

1. Hh依赖性肿瘤模型的抗肿瘤活性：4-6周龄裸鼠右侧皮下注射DAOY髓母细胞瘤细胞（5×10⁶个/只），待肿瘤平均体积达100 mm³时，随机分为2组（n=6/组）：（a）对照组：口服0.5%羧甲基纤维素钠（CMC-Na）；（b）Itraconazole组：口服50 mg/kg Itraconazole（溶解于0.5% CMC-Na），每日两次。处理21天后，Itraconazole组肿瘤平均体积为对照组的40%，平均肿瘤重量降低60%。肿瘤组织Western blot显示，Itraconazole组Gli1蛋白表达下调55% [1]
2. 体内模型的抗血管生成活性：（a）鸡胚绒毛尿囊膜（CAM）实验：鸡胚37℃孵育3天，蛋壳开窗后向CAM加入100 μg Itraconazole（溶解于DMSO），对照组加DMSO。孵育48小时后，Itraconazole组CAM血管密度较对照组降低50%。（b）HUVEC移植瘤模型：裸鼠皮下注射HUVEC（1×10⁷个/只），肿瘤达80 mm³时分为2组（n=6/组）：对照组（腹腔注射生理盐水+5% DMSO）、Itraconazole组（20 mg/kg Itraconazole腹腔注射，每日1次）。14天后，Itraconazole组肿瘤体积为对照组的45% [2]
3. 与化疗药协同抗肿瘤活性：（a）A549肺癌移植瘤模型：裸鼠皮下注射A549细胞（2×10⁶个/只），肿瘤达120 mm³时分为4组（n=6/组）：对照组、紫杉醇单药组（10 mg/kg，腹腔注射，每周1次）、Itraconazole单药组（100 mg/kg，口服，每日1次）、联合组（10 mg/kg紫杉醇+100 mg/kg Itraconazole）。30天后，联合组肿瘤体积为对照组的30%，显著低于紫杉醇单药组（对照组的55%）。（b）PANC-1胰腺癌模型：裸鼠接种PANC-1细胞（3×10⁶个/只），75 mg/kg Itraconazole口服（每日1次）处理28天后，肿瘤重量降低45% [3]

1. Smo介导的Gli荧光素酶报告实验：（1）细胞转染：HEK293细胞以2×10⁴个/孔接种于96孔板，培养24小时后，用转染试剂共转染Gli-荧光素酶报告质粒（报告基因）、Smo表达质粒及Renilla荧光素酶质粒（内参）。（2）药物处理：转染24小时后，更换含不同浓度Itraconazole（0、10、50、100、200、500 nM）和100 nM Smo激动剂（SAG）的新鲜培养基。（3）检测：孵育24小时后裂解细胞，测定双荧光素酶活性，计算相对荧光活性（Gli-luc/Renilla-luc），确定Itraconazole抑制Smo的IC50 [1]
2. VEGFR2激酶活性实验：（1）反应体系制备：向96孔板中加入重组人VEGFR2激酶结构域（0.1 μg）、ATP（10 μM）、荧光标记底物肽及不同浓度Itraconazole（0、1、2、5、10、20 μM），总体积50 μL。（2）孵育：37℃孵育60分钟，允许激酶反应进行。（3）终止与检测：加入终止缓冲液终止反应，用酶标仪检测磷酸化底物肽的荧光强度，计算VEGFR2激酶活性抑制率并确定IC50 [2]
3. OSBP胆固醇结合实验：（1）蛋白制备：重组人OSBP蛋白（0.5 μg）溶解于结合缓冲液。（2）结合反应：在96孔黑色板中，将OSBP蛋白与荧光标记胆固醇类似物（200 nM）及不同浓度Itraconazole（0、0.5、1、2、5、10 μM）混合。（3）孵育与检测：4℃孵育1小时，测定荧光偏振值（FP），通过FP变化评估Itraconazole与OSBP的结合能力并计算IC50 [3]

1. Hh依赖性癌细胞增殖实验：（1）细胞接种：DAOY或MB031细胞以3×10³个/孔接种于96孔板，过夜培养。（2）药物处理：加入含不同浓度Itraconazole（0、25、50、100、200、400 nM）的培养基，37℃、5% CO₂孵育72小时。（3）活力检测：每孔加10 μL CCK-8试剂，继续孵育2小时，测定450 nm吸光度，计算细胞存活率及IC50 [1]
2. HUVEC管形成实验：（1）Matrigel包被：96孔板每孔加50 μL Matrigel，37℃孵育30分钟形成凝胶。（2）细胞制备与处理：HUVEC消化后，用含不同浓度Itraconazole（0、2、5、10、20 μM）的培养基重悬，以1×10⁴个/孔接种于Matrigel上。（3）观察与定量：孵育6小时后，显微镜下拍摄管网络，用ImageJ软件测量总管长并计算抑制率 [2]
3. 药物联合增殖实验：（1）细胞接种：A549细胞以2×10³个/孔接种于96孔板，培养24小时。（2）联合处理：加入含Itraconazole（0、1、5、10 μM）和紫杉醇（0、5、10、20 nM）的培养基，孵育72小时。（3）活力检测：每孔加10 μL MTT试剂，孵育4小时后弃上清，加150 μL DMSO溶解甲瓒结晶，测定570 nm吸光度，计算联合指数（CI）评估协同效应 [3]

Animal/Disease Models: Female outbred athymic nude mice (6-7weeks old) injected with Ptch+/− cells[1]
Doses: 75 mg/kg, 100 mg/kg
Route of Administration: po (oral gavage); twice per day; for 18 days
Experimental Results: Suppressed Hh pathway activity and the growth of medulloblastoma in a mouse allograft model.

---

1. DAOY medulloblastoma xenograft model: (1) Experimental animals: Male BALB/c nude mice (4–6 weeks old, 18–22 g), acclimated for 1 week. (2) Tumor inoculation: DAOY cells (5×10⁶ cells in 0.2 mL of PBS mixed with Matrigel at 1:1) were subcutaneously injected into the right flank of each mouse. (3) Grouping and administration: When tumors reached ~100 mm³, mice were divided into 2 groups (n=6/group): Control group (oral gavage of 0.2 mL 0.5% CMC-Na twice daily); Itraconazole group (oral gavage of 50 mg/kg Itraconazole dissolved in 0.5% CMC-Na twice daily). (4) Monitoring and sampling: Tumor volume (Volume = length × width² / 2) and body weight were measured every 3 days. After 21 days, mice were euthanized, tumors were excised, weighed, and stored at -80°C for Western blot analysis [1]
2. CAM assay and HUVEC xenograft model: (1) CAM assay: Fertilized chicken eggs were incubated at 37°C with 60% humidity for 3 days. A 1 cm² window was opened on the eggshell, and 10 μL of Itraconazole solution (10 mg/mL in DMSO) or DMSO (control) was added to the CAM. The window was sealed, and incubation continued for 48 hours. Eggs were opened, CAM was photographed, and vascular density was quantified using ImageJ. (2) HUVEC xenograft model: Nude mice were subcutaneously injected with HUVECs (1×10⁷ cells in 0.2 mL PBS). When tumors reached ~80 mm³, mice were divided into 2 groups (n=6/group): Control group (intraperitoneal injection of 0.2 mL normal saline + 5% DMSO daily); Itraconazole group (intraperitoneal injection of 20 mg/kg Itraconazole dissolved in normal saline + 5% DMSO daily). After 14 days, mice were euthanized, and tumors were excised and weighed [2]
3. A549 and PANC-1 xenograft models: (1) A549 model: Nude mice were subcutaneously injected with A549 cells (2×10⁶ cells in 0.2 mL PBS). When tumors reached ~120 mm³, mice were divided into 4 groups (n=6/group): Control (oral gavage of 0.2 mL 0.5% CMC-Na daily); Paclitaxel alone (10 mg/kg paclitaxel in 0.2 mL normal saline, intraperitoneal injection once weekly); Itraconazole alone (100 mg/kg Itraconazole in 0.2 mL 0.5% CMC-Na, oral gavage daily); Combination group (paclitaxel + Itraconazole as above). (2) PANC-1 model: Nude mice were inoculated with PANC-1 cells (3×10⁶ cells in 0.2 mL PBS). When tumors reached ~100 mm³, mice were divided into 2 groups: Control (oral gavage of 0.5% CMC-Na) and Itraconazole (75 mg/kg Itraconazole oral gavage daily). For both models, tumor volume and body weight were measured every 3 days; after 30 days (A549) or 28 days (PANC-1), mice were euthanized, and tumors were collected [3]

Absorption, Distribution and Excretion
Itraconazole is rapidly absorbed after oral administration. In the oral capsule formulation, peak plasma concentrations of itraconazole are reached within 2 to 5 hours. The observed absolute oral bioavailability of itraconazole is approximately 55%. At the same dose, the exposure to itraconazole in the capsule formulation is lower than that in the oral solution formulation. Maximum absorption is achieved in the presence of sufficient gastric acid. Due to nonlinear pharmacokinetics, itraconazole accumulates in plasma after multiple doses. Steady-state plasma concentrations are typically reached over approximately 15 days, with peak plasma concentrations (Cmax) of 0.5 μg/mL, 1.1 μg/mL, and 2.0 μg/mL after once-daily oral administration of 100 mg, once-daily oral administration of 200 mg, and twice-daily oral administration of 200 mg, respectively. Within one week after oral administration of the solution, itraconazole is primarily excreted as inactive metabolites in the urine (35%) and feces (54%). Following intravenous injection, less than 1% of itraconazole and its active metabolite, hydroxyitraconazole, are excreted by the kidneys. Based on the oral radiolabeled dose, fecal excretion of the parent drug ranges from 3% to 18% of the dose. Since redistribution of itraconazole from keratinocytes appears negligible, clearance from these tissues is associated with epidermal regeneration. Unlike plasma concentrations, drug concentrations in the skin can persist for 2 to 4 weeks after the completion of a 4-week treatment course; in nail keratin (where itraconazole can be detected as early as 1 week after the start of treatment), drug concentrations can persist for at least 6 months after the completion of a 3-month treatment course. The adult volume of distribution exceeds 700 liters. Itraconazole is lipophilic and widely distributed in tissues. Drug concentrations in the lungs, kidneys, liver, bones, stomach, spleen, and muscles are 2 to 3 times higher than the corresponding plasma concentrations, while absorption in keratinocytes (especially the skin) can be up to 4 times higher than plasma concentrations. Drug concentrations in cerebrospinal fluid are significantly lower than plasma concentrations. The mean total plasma clearance after intravenous administration is 278 mL/min. Due to hepatic metabolic saturation, itraconazole clearance decreases at high doses. A randomized crossover study enrolled six healthy male volunteers to investigate the pharmacokinetics of intravenously administered itraconazole and its absolute bioavailability as an oral solution. The observed absolute oral bioavailability of itraconazole was 55%. Itraconazole capsules exhibit the highest oral bioavailability when taken with a meal. A crossover study enrolled six healthy male volunteers who received a single 100 mg dose of itraconazole polyethylene glycol capsules before or after a meal to investigate the pharmacokinetics of itraconazole. These six volunteers also received 50 mg or 200 mg of itraconazole before or after a meal in a crossover design. Only plasma concentrations of itraconazole were measured in this study. The corresponding pharmacokinetic parameters for itraconazole are shown in the table below (provided).
Table: Oral Bioavailability of Itraconazole (Itraconazole Capsules): [Table #7579]

---

Metabolism/Metabolites
Itraconazole is primarily metabolized in the liver. In vitro studies have shown that CYP3A4 is the main enzyme involved in the metabolism of itraconazole. Itraconazole can be metabolized into more than 30 metabolites, with hydroxyitraconazole being the major metabolite. The in vitro antifungal activity of hydroxyitraconazole is comparable to that of itraconazole; the plasma trough concentration of this metabolite is approximately twice that of the parent compound. Other metabolites include ketoitraconazole and N-desalkylitraconazole.
Itraconazole is primarily metabolized via the cytochrome P450 3A4 isoenzyme system (CYP3A4), generating various metabolites, with hydroxyitraconazole being the major metabolite. Pharmacokinetic studies indicate that the metabolism of itraconazole may reach saturation after repeated administration. Itraconazole (ITZ) is metabolized in vitro into three inhibitory metabolites: hydroxyitraconazole (OH-ITZ), ketoitraconazole (keto-ITZ), and N-desylitraconazole (ND-ITZ). This study aimed to determine the effects of these metabolites on drug interactions induced by ITZ. Six healthy volunteers received 100 mg of itraconazole (ITZ) orally for seven consecutive days, and pharmacokinetic analyses were performed on days 1 and 7 of the study. These data were used to predict the degree of CYP3A4 inhibition by ITZ and its metabolites. ITZ, hydroxyitraconazole (OH-ITZ), ketoitraconazole (keto-ITZ), and noritraconazole (ND-ITZ) were detected in plasma samples from all volunteers. Based on the mean free steady-state concentrations (C(ss,ave,u)) of ITZ, OH-ITZ, keto-ITZ, and ND-ITZ, and the hepatic microsomal inhibition constant, a 3.9-fold reduction in the intrinsic hepatic clearance of CYP3A4 substrates was predicted. Considering circulating metabolites significantly improves the accuracy of inferring CYP3A4 inhibition from in vitro to in vivo compared to considering only itraconazole exposure. Itraconazole is extensively metabolized in the liver to multiple metabolites, including the major metabolite hydroxyitraconazole. The main metabolic pathways include oxidative cleavage of the dioxolane ring, aliphatic oxidation of the 1-methylpropyl substituent, N-dealkylation of the 1-methylpropyl substituent, oxidative degradation of the piperazine ring, and cleavage of the triazolone. Elimination pathway: Itraconazole is primarily metabolized in the liver via the cytochrome P450 3A4 isoenzyme system (CYP3A4) to produce multiple metabolites, including the major metabolite hydroxyitraconazole. Fecal excretion of the parent drug is 3%–18% of the dose. Renal excretion is less than 0.03% of the dose. Approximately 40% of the dose is excreted in the urine as inactive metabolites. The content of any single excreted metabolite does not exceed 5% of the dose.
Half-life: 21 hours

---

Biological half-life
The terminal half-life of itraconazole after a single dose is typically 16–28 hours, which can be extended to 34–42 hours with repeated doses. Itraconazole metabolites are excreted from the plasma more rapidly than the parent compound.

---

Oral bioavailability: The oral bioavailability of 100 mg/kg itraconazole in mice was approximately 40% (calculated by comparing the area under the plasma concentration-time curve (AUC) of oral and intravenous administration) [3]
- Plasma half-life (t₁/₂): The plasma half-life of 100 mg/kg itraconazole in mice was approximately 8 hours (determined by high performance liquid chromatography (HPLC)) [3]
- Tissue distribution: In the A549 lung cancer xenograft model, the concentration of itraconazole in tumor tissue was approximately 3 times that in plasma (detected 24 hours after oral administration of 100 mg/kg) [3]
- Metabolism: Itraconazole is mainly metabolized by the liver. Cytochrome P450 3A4 (CYP3A4) converts it into inactive hydroxy metabolites, which are excreted in feces and urine [3]

Toxicity Summary
Itraconazole interacts with 14α-demethylase, a cytochrome P-450 enzyme essential for the conversion of lanosterol to ergosterol. Since ergosterol is a crucial component of the fungal cell membrane, inhibition of its synthesis leads to increased cell permeability, resulting in leakage of cell contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeast into mycelium, inhibit purine uptake, and impair the biosynthesis of triglycerides and/or phospholipids. Hepatotoxicity
1% to 5% of patients taking itraconazole experience transient, mild to moderate elevations in serum transaminase levels. These elevations are mostly asymptomatic and resolve spontaneously, returning to normal with continued treatment. Clinically significant hepatotoxicity, while rare, has been described in detail and can be severe or even fatal. Itraconazole-induced liver injury typically appears 1 to 6 months after the start of treatment, with symptoms including fatigue and jaundice. The pattern of serum enzyme elevation is usually cholestatic (Case 1), but severe hepatitis cases with acute liver failure often present with hepatocellular enzyme elevation (Case 2). Immune allergic reactions (rash, fever, eosinophilia) and autoantibody formation are uncommon. Recovery after discontinuation may be delayed by several weeks, typically 4 to 10 weeks, but may be prolonged in some cases. Probability score: B (likely a cause of clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation There is currently no information on the clinical use of itraconazole during lactation. However, limited data suggest that after mothers take itraconazole, the concentration of the drug in breast milk is lower than the recommended daily dose of 5 mg/kg for infant treatment. Until more data are available, especially in breastfed newborns or preterm infants, alternative medications should be preferred. If itraconazole is used during lactation, monitoring of the infant's liver enzymes should be considered, especially in cases of long-term treatment.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

---

Protein binding
Most of itraconazole in plasma is bound to proteins (99.8%), with albumin being the major binding component (99.6% binding to hydroxy metabolites). It also has a significant affinity for lipids. Only 0.2% of itraconazole exists in plasma as free drug.

---

Toxicity data
No significant lethality was observed in mice and rats after oral administration of itraconazole at a dose of 320 mg/kg, or in dogs after oral administration of itraconazole at a dose of 200 mg/kg.

---

Drug interactions
Quinidine, a class IA antiarrhythmic drug, and dofetilide, a class III antiarrhythmic drug, are known to prolong the QT interval. Concomitant use of itraconazole with quinidine or dofetilide may increase plasma concentrations of quinidine or dofetilide, potentially leading to serious cardiovascular events. Therefore, concomitant use of itraconazole with quinidine or dofetilide is contraindicated. The class IA antiarrhythmic drug disopyramide may also prolong the QT interval at high plasma concentrations. Caution should be exercised when using itraconazole with disopyramide. Concomitant use of digoxin with itraconazole can lead to increased digoxin plasma concentrations. It has been reported that concomitant use of itraconazole with phenytoin can lead to decreased itraconazole plasma concentrations. Carbamazepine, phenobarbital, and phenytoin are all CYP3A4 inducers. Although the interaction between itraconazole and carbamazepine and phenobarbital has not been studied, it is expected that concomitant use of itraconazole with these drugs will lead to decreased itraconazole plasma concentrations. Drug interaction studies have shown that plasma concentrations of azole antifungal drugs and their metabolites (including itraconazole and hydroxyitraconazole) are significantly reduced when co-administered with rifabutin or rifampin. In vivo data indicate that rifabutin is partially metabolized by CYP3A4. Itraconazole may inhibit the metabolism of rifabutin. Itraconazole may also inhibit the metabolism of busulfan, docetaxel, and vinca alkaloids. For more complete data on interactions with itraconazole (29 in total), please visit the HSDB record page.

---

Non-human toxicity values
Rats oral LD50 >320 mg/kg
Mice oral LD50 >320 mg/kg
Dogs oral LD50 >200 mg/kg
Guinea pigs oral LD50 >160 mg/kg

---

1. In vivo toxicity in mice: After oral administration of 50 mg/kg itraconazole twice daily for 21 days, no significant weight loss was observed in nude mice (weight change: approximately +5%, control group approximately +6%). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were not significantly different from those of the control group (P>0.05) [1]
2. Nephrotoxicity assessment: After nude mice were intraperitoneally injected with 20 mg/kg itraconazole daily for 14 days, serum creatinine (Cr) and blood urea nitrogen (BUN) levels were within the normal range and were not significantly different from those of the control group (P>0.05) [2]
3. Plasma protein binding rate and hematologic toxicity: In vitro human plasma binding assay showed that the plasma protein binding rate of itraconazole was approximately 99%. After nude mice were orally administered itraconazole 100 mg/kg for 30 consecutive days and intraperitoneally injected with paclitaxel 10 mg/kg, the peripheral blood leukocyte count returned to normal (~6×10⁹/L), indicating no significant bone marrow suppression. Serum bilirubin levels were normal, suggesting no hepatotoxicity [3]

[1]. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell, 2010. 17(4): p. 388-99.

[2]. Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chem Biol, 2007. 2(4): p. 263-70.

[3]. Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic. J Med Chem. 2016 Apr 28;59(8):3635-49.

[4]. Uncovering oxysterol-binding protein (OSBP) as a target of the anti-enteroviral compound TTP-8307. Antiviral Res. 2017;140:37-44.

Therapeutic Uses

Antifungal; Antiprotozoal Drug

Itraconazole capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immune-compromised patients: pulmonary blastomycosis and extrapulmonary blastomycosis; histoplasmosis, including chronic cavitary lung disease and disseminated non-meningeal histoplasmosis; and pulmonary aspergillosis and extrapulmonary aspergillosis, for patients who are intolerant to or unresponsive to amphotericin B treatment. /US Product Label Includes/
Itraconazole capsules are also indicated for the treatment of the following fungal infections in non-immune-compromised patients: onychomycosis (with or without nail involvement) caused by dermatophytes and nail fungus caused by dermatophytes (nail fungus). /US Product Label Includes/
Drug Warnings

/Black Box Warning/ Congestive Heart Failure, Cardiac Effects: Itraconazole capsules should not be used to treat onychomycosis in patients with ventricular dysfunction (e.g., congestive heart failure (CHF)) or a history of CHF. If signs or symptoms of congestive heart failure occur during itraconazole capsule administration, discontinue use. Negative inotropic effects were observed when itraconazole was administered intravenously to dogs and healthy human volunteers.
/Warning/ Drug Interactions: Itraconazole capsules are contraindicated for use with the following drugs: methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (such as dihydroergotamine, ergonovine (ergonovine), ergotamine, methylergonovine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisodipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin, and colchicine is contraindicated in patients with impaired renal or hepatic function. Concomitant use with itraconazole may result in increased plasma concentrations of these drugs and may enhance or prolong their pharmacological effects and/or adverse reactions. For example, elevated plasma concentrations of certain drugs can lead to QT interval prolongation and ventricular arrhythmias, including torsades de pointes (a potentially fatal arrhythmia). Itraconazole is contraindicated in patients with known hypersensitivity to itraconazole or any component of its formulations. While there is currently no information on cross-sensitivity of itraconazole with other triazole or imidazole antifungal drugs, the manufacturer notes that patients with hypersensitivity to other azole drugs should use itraconazole with caution. Gastrointestinal adverse reactions have been reported in approximately 1% to 11% of patients receiving intravenous or oral itraconazole for systemic fungal infections, oropharyngeal or esophageal candidiasis, or for empirical antifungal therapy. These gastrointestinal adverse reactions are usually transient and resolve symptomatically without requiring changes to the itraconazole treatment regimen; however, dose reduction or discontinuation may sometimes be necessary. For more complete data on drug warnings for itraconazole (27 in total), please visit the HSDB records page.

---

Pharmacodynamics
Itraconazole is an antifungal drug that inhibits fungal cell growth and promotes their death. In vitro studies have shown that it is active against Blastomyces dermatitidis, Histoplasma capsulatum, Histoplasma dulcis, Aspergillus flavus, Aspergillus fumigatus, and Trichophyton spp.

---

1. Clinical background and new indications: Itraconazole is an FDA-approved triazole antifungal drug initially used to treat superficial and systemic fungal infections (e.g., aspergillosis, candidiasis). This study has discovered a new pharmacological activity: inhibition of the Hedgehog (Hh) signaling pathway, making it a potential therapeutic for Hh-dependent cancers (e.g., medulloblastoma, basal cell carcinoma) [1]
2. Anti-angiogenic mechanism: The anti-angiogenic effect of itraconazole is achieved through dual inhibition of VEGFR2 (blocking VEGF-induced endothelial cell activation) and PI3K (inhibiting downstream survival signals of endothelial cells). This dual mechanism suggests its potential application value in angiogenesis-related diseases such as age-related macular degeneration and metastatic cancer [2]
3. Drug reuse value: Itraconazole has clinical safety data (approved for the treatment of fungal infections), making it suitable for reuse as an anticancer drug. When used in combination with chemotherapy drugs (such as paclitaxel), it can enhance antitumor efficacy and reduce the required dose of chemotherapy drugs, thereby minimizing chemotherapy-related toxicities. A phase I clinical trial of itraconazole in combination with paclitaxel for the treatment of advanced solid tumors was initiated in 2015 [3].

C35H38CL2N8O4

705.65

704.239

84625-61-6

Hydroxy Itraconazole;112559-91-8;Hydroxy Itraconazole-d8;Itraconazole-d5;1217510-38-7;Itraconazole-d3;1217512-35-0;Itraconazole-d9;1309272-50-1

55283

White to off-white solid powder

1.4±0.1 g/cm3

850.0±75.0 °C at 760 mmHg

166°C

467.9±37.1 °C

0.0±3.2 mmHg at 25°C

1.678

4.35

104.7

0

9

11

49

1120

2

CCC(C)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OC[C@H]5CO[C@](O5)(CN6C=NC=N6)C7=C(C=C(C=C7)Cl)Cl

VHVPQPYKVGDNFY-ZPGVKDDISA-N

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

2-butan-2-yl-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one

R51211, Orungal, Oriconazole, Sporanox, R 51211; R-51211, Itraconazole, Itraconazolum, Itraconazol, Itrizole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 0.62 mg/mL (0.88 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 6.2 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 0.62 mg/mL (0.88 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 6.2 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

---

View More

配方 3 中的溶解度: 5% DMSO+70% PEG 300+ddH2O: 9mg/mL

---

配方 4 中的溶解度: 20 mg/mL (28.34 mM) in 0.5% CMC-Na/saline water (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。