H₁ Receptor

Fexofenadine（1-100 µM；1 小时）以剂量依赖性方式抑制鼻成纤维细胞中 IL-6 蛋白的表达[2]。 Fexofenadine（1-100 µM；1 小时）可阻断组胺诱导的鼻成纤维细胞中磷酸化 p38 的激活，但对 pERK 或 pJNK 没有影响[2]。 Western Blot 分析[2] 细胞系：鼻成纤维细胞 浓度：100 μM 孵育时间：1 小时 结果：阻断组胺诱导的鼻成纤维细胞中 pp38 的激活，显示组胺诱导的 IL-6 产生是由 p38 途径介导的。

盐酸非索非那定（口服；5-20 mg/kg；每日一次；3 周）可抑制感染旋毛虫的 C57BL/6 小鼠的嗜酸性粒细胞增多和全身过敏反应[1]。动物模型：感染旋毛虫的C57BL/6小鼠[1] 剂量：5、10和20mg/kg 给药方法：口服；口服；口服；口服；口服。 5、10和20毫克/公斤；每天一次; 3 周 结果：以剂量依赖性方式抑制嗜酸性粒细胞增多。抑制直肠温度的下降（p<0.01），这是全身过敏反应的标志。

细胞系：鼻成纤维细胞
浓度：100 μM
孵育时间：1 小时
结果：阻断组胺诱导的鼻成纤维细胞中 pp38 的激活，显示组胺诱导的 IL-6 产生是由 p38 途径介导的。

C57BL/6 mice infected with Trichinella spiralis
5, 10 and 20 mg/kg
Oral administration; 5, 10 and 20 mg/kg; once daily; 3 weeks

Absorption, Distribution and Excretion
Fexofenadine is rapidly absorbed following oral administration and its absolute bioavailability is approximately 33%. The Tmax following oral administration is approximately 1-3 hours. The steady-state AUCss(0-12h) and Cmax following twice daily dosing of 60mg are 1367 ng/mL.h and 299 ng/mL, respectively. Fexofenadine AUC is decreased by >20% when coadministered with fruit juices (e.g. apple, orange, grapefruit) due to their inhibition of OATP transporters - for this reason, prescribing information recommends administering fexofenadine only with water. Similarly, coadministration of fexofenadine with a high-fat meal appears to decrease AUC and Cmax by >20%.
Approximately 80% of an ingested dose is eliminated in the feces, likely largely unchanged due to fexofenadine's limited metabolism, and 11% is eliminated in the urine. The principal pathways of fexofenadine elimination are biliary and renal.
The volume of distribution is approximately 5.4-5.8 L/kg.
The oral clearance of fexofenadine is approximately 50.6 L/h and the renal clearance is approximately 4.32 L/h.
Fexofenadine hydrochloride is rapidly absorbed from the GI tract following oral administration. Following oral administration of two 60-mg fexofenadine hydrochloride capsules, peak plasma concentrations are achieved in about 2.6 hours. Following oral administration of a single 60-mg capsule or 60- or 180-mg conventional tablet in healthy individuals, mean peak plasma concentrations were 131, 142, and 494 ng/mL, respectively. In healthy men, peak plasma concentrations of 167 ng/mL were achieved within 1.42 hours following oral administration of 60-mg fexofenadine hydrochloride doses every 12 hours for 9 doses.
Following oral administration of fexofenadine hydrochloride capsules in fasting children (mean age: 8-11.6 years) with a history of allergic rhinitis with or without mild asthma, peak plasma fexofenadine concentrations of about 178 or 286 ng/mL were attained in approximately 2.4 hours after a 30- or 60-mg dose, respectively.
Following oral administration of a 60-mg dose of fexofenadine hydrochloride, the AUC was 56% greater in children 7-12 years of age with allergic rhinitis than in healthy adults. Plasma exposure in children receiving 30 mg of fexofenadine hydrochloride is similar to that of adults receiving 60 mg of the drug. Limited data indicate that peak plasma fexofenadine concentrations in adolescents (12-16 years of age) were similar to those in adults, while peak plasma concentrations in geriatric adults (65 years of age and older) were 99% greater than in healthy individuals younger than 65 years of age. AUC also was higher in geriatric adults (65-80 years of age) than in younger adults (19-45 years of age)...
Peak plasma concentrations of fexofenadine were 87 and 111% higher in patients with mild (creatinine clearance of 41-80 mL/minute) to severe (creatinine clearance of 11-40 mL/minute) renal impairment, respectively, compared with those observed in healthy adults. In patients undergoing dialysis (creatinine clearance of 10 mL/minute or less), peak plasma concentrations of fexofenadine were 82% higher than in healthy adults.
For more Absorption, Distribution and Excretion (Complete) data for FEXOFENADINE (12 total), please visit the HSDB record page.

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Metabolism / Metabolites
Fexofenadine is very minimally metabolized, with only 5% of an ingested dose undergoing hepatic metabolism. The only identified metabolites are a methyl ester of fexofenadine (3.6% of the total dose) and MDL 4829 (1.5% of the total dose). The enzymes responsible for this metabolism have not been elucidated.
About 5% of a single oral dose of fexofenadine is metabolized.
Negligible amounts of fexofenadine (about 0.5-1.5% of a dose) are metabolized in the liver by the cytochrome P-450 microsomal enzyme system to an inactive metabolite, while about 3.5% of a fexofenadine dose is metabolized by a second metabolic pathway (unrelated to the cytochrome P-450 microsomal enzyme system) to the methyl ester derivative of fexofenadine. The methyl ester metabolite of fexofenadine is found only in feces, and it has been suggested that the intestinal flora probably are involved in this metabolism.
Approximately 5% of the total dose is metabolized, by cytochrome P450 3A4 and by intestinal microflora.
Half Life: 14.4 hours

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Biological Half-Life
The terminal elimination half-life is approximately 11-15 hours.
Following oral administration of 60 mg of fexofenadine hydrochloride twice daily in healthy individuals, the mean elimination half-life of the drug at steady state reportedly is about 14.4-14.6 hours; mean elimination half-life reportedly was similar in geriatric adults (65 years of age or older) who received a single 80-mg oral dose of fexofenadine hydrochloride.
... Elimination half-life was about 18 hours in fasting children (mean age: 8-11.6 years) who received single oral 30- or 60-mg doses of fexofenadine hydrochloride as capsules.
In patients with mild (creatinine clearance of 41-80 mL/minute) to severe (creatinine clearance of 11-40 mL/minute) renal impairment, mean elimination half-lives were 59 and 72% longer than those observed in healthy individuals, respectively.
In patients undergoing dialysis (creatinine clearance of 10 mL/minute or less), elimination half-life was 31% longer than in healthy individuals.

Toxicity Summary
Like other H1-blockers, Fexofenadine competes with free histamine for binding at H1-receptors in the GI tract, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine. Fexofenadine exhibits no anticholinergic, antidopaminergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects.

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Interactions
Increased concentrations of fexofenadine have been reported in 2 controlled drug interaction studies in healthy individuals receiving 120 mg of fexofenadine hydrochloride twice daily concomitantly with erythromycin dosages of 500 mg every 8 hours or ketoconazole 400 mg once daily. In these studies, area under the plasma-concentration time curve (AUC) of fexofenadine increased by 109 or 164% following concomitant administration with erythromycin or ketoconazole, respectively, while peak plasma concentrations of fexofenadine increased by 82 or 135%, respectively. However, no clinically important adverse effects or changes in the QT interval corrected for rate (QTc) were reported after concomitant administration of erythromycin or ketoconazole with fexofenadine.
Administration of a single 120-mg dose (2 capsules of 60 mg) of fexofenadine hydrochloride within 15 minutes of administration of an aluminum and magnesium hydroxides antacid (Maalox) decreased the AUC and peak plasma concentration of fexofenadine by 41 and 43%, respectively. Therefore, the manufacturer states that fexofenadine (alone or in fixed combination with pseudoephedrine hydrochloride) should not be taken closely in time with antacids containing aluminum and magnesium.
Fruit (grapefruit, orange, apple) juices may reduce bioavailability and systemic exposure of fexofenadine. In clinical studies, the size of wheal and flare was substantially larger when fexofenadine hydrochloride was administered with grapefruit juice or orange juice compared with water; based on literature reports, the same effects may be extrapolated to other fruit juices such as apple juice. The clinical importance of these observations is unknown. Based on a population pharmacokinetic analysis of combined data from the studies using concomitant grapefruit juice or orange juice with data from a bioequivalence study, bioavailability of fexofenadine was reduced by 36%. Therefore, to maximize the effects of fexofenadine, the manufacturer recommends that the drug be administered with water.

[1]. The effects of fexofenadine on eosinophilia and systemic anaphylaxis in mice infected with Trichinella spiralis. Int Immunopharmacol. 2004 Mar;4(3):367-75.

[2]. Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-κB Pathways in Nasal Fibroblasts. Allergy Asthma Immunol Res. 2014 Nov;6(6):567-72.

[3]. Vectorial transport of fexofenadine across Caco-2 cells: involvement of apical uptake and basolateral efflux transporters. Mol Pharm. 2011 Oct 3;8(5):1677-86.

Therapeutic Uses
Histamine H1 antagonists
Antihistaminic
Fexofenadine is indicated to relieve symptoms that are associated with seasonal allergic rhinitis, such as sneezing;rhinorrhea; itchy eyes, nose and throt; and red watery eyes. /Included in US product label/
Fexofenadine is indicated for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria. It significantly reduces pruritus and the number of wheals. /Included in US product label/

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Drug Warnings
In controlled clinical studies in patients 12 years of age and older with allergic rhinitis receiving oral fexofenadine hydrochloride dosages of 60 mg twice daily or placebo, drowsiness or fatigue occurred in 1.3% of patients, compared with 0.9% of those receiving placebo. In these studies in patients receiving fexofenadine hydrochloride dosages of 180 mg once daily (as conventional tablets) or placebo, headache was reported in 10.6 or 7.5% of patients, respectively. In controlled studies in children 6-11 years of age with seasonal allergic rhinitis receiving fexofenadine hydrochloride dosages of 30 mg twice daily or placebo, headache was reported in 7.2 or 6.6% of patients, respectively, while pain was reported in 2.4 or 0.4% of patients, respectively.
Sleep disorder, insomnia, or paroniria has occurred in patients receiving fexofenadine hydrochloride.
During controlled clinical studies, nausea and dyspepsia were reported in 1.6 and 1.3%, respectively, of patients receiving oral fexofenadine hydrochloride dosages of 60 mg twice daily versus 1.5 and 0.6%, respectively, of those receiving placebo.
Clinical data from over 2000 patients indicate that fexofenadine hydrochloride lacks the cardiotoxic potential of its parent drug terfenadine. In 714 patients with seasonal allergic rhinitis, fexofenadine hydrochloride dosages of 60-240 mg twice daily were not associated with statistically significant mean increases in the QT interval corrected for rate (QTc) in controlled clinical studies. In addition, in 231 healthy individuals, fexofenadine hydrochloride dosages of 240 mg given once daily for 1 year also were not associated with statistically significant increases in the mean QTc. Even at dosages exceeding these (e.g., up to 400 mg twice daily for 6 days in 40 patients, up to 690 mg twice daily for about 1 month in 32 patients, up to 800 mg given in a single dose in 87 patients), statistically significant mean increases in the QTc or other ECG abnormalities have not been reported in healthy adults or patients with seasonal allergic rhinitis.
For more Drug Warnings (Complete) data for FEXOFENADINE (15 total), please visit the HSDB record page.

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Pharmacodynamics
Fexofenadine relieves allergy symptoms by antagonizing the actions of histamine, an endogenous compound predominantly responsible for allergic symptomatology. The relatively long duration of action of fexofenadine (approximately 24 hours) allows for once or twice daily dosing, and its rapid absorption allows for an onset of action within 1-3 hours. Fexofenadine should not be taken with fruit juice, as this may impair its absorption.

C32H39NO4

501.65636

501.287

C, 76.61; H, 7.84; N, 2.79; O, 12.76

83799-24-0

Fexofenadine hydrochloride; 153439-40-8; Fexofenadine-d6; 548783-71-7; Fexofenadine-d6 Methyl Ester; 1286458-00-1; Fexofenadine-d3; Fexofenadine-d10; 1215900-18-7

3348

Off-white to light yellow solid powder

1.2±0.1 g/cm3

697.3±55.0 °C at 760 mmHg

218-220ºC

375.5±31.5 °C

0.0±2.3 mmHg at 25°C

1.597

4.8

81

3

5

10

37

678

0

O=C(C(C)(C)C1C=CC(C(CCCN2CCC(C(C3C=CC=CC=3)(C3C=CC=CC=3)O)CC2)O)=CC=1)O

RWTNPBWLLIMQHL-UHFFFAOYSA-N

InChI=1S/C32H39NO4/c1-31(2,30(35)36)25-17-15-24(16-18-25)29(34)14-9-21-33-22-19-28(20-23-33)32(37,26-10-5-3-6-11-26)27-12-7-4-8-13-27/h3-8,10-13,15-18,28-29,34,37H,9,14,19-23H2,1-2H3,(H,35,36)

2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid

Telfast; Fexofenadine; Allegra; Carboxyterfenadine; MDL 16.455

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。