Fexofenadine HCl (formerly MDL-16455A; Allegra; Terfenidine carboxylate; Telfast) is a potent histamine H1 receptor antagonist (antihistamine agent) used in the treatment of allergy symptoms such as hay fever, nasal congestion, and urticaria. Fexofenadine belongs to the second generation of antihistamines because, in contrast to first-generation antihistamines, it is less able to sedate people by crossing the blood-brain barrier.Fexofenadine has an IC50 value of 95.5 nM and demonstrates a strong, concentration-dependent anti-anaphylactic effect. For the 5-HT2A receptors from the rat caudal artery with a pA2 of 5.2, fexofenadine only exhibits a weak competitive antagonist behavior. On the P-gp-mediated secretion of Fexofenadine, verapamil's half-life (IC50) is 8.44 mM.

Physicochemical Properties

Molecular Formula	C32H40CLNO4
Molecular Weight	538.12
Exact Mass	537.264
Elemental Analysis	C, 71.42; H, 7.49; Cl, 6.59; N, 2.60; O, 11.89
CAS #	153439-40-8
Related CAS #	Fexofenadine; 83799-24-0; Fexofenadine-d6; 548783-71-7; Fexofenadine-d10 hydrochloride; 1215821-44-5
PubChem CID	63002
Appearance	White to off-white solid powder
Melting Point	148-150oC
LogP	6.25
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	10
Heavy Atom Count	38
Complexity	678
Defined Atom Stereocenter Count	0
SMILES	Cl[H].O([H])C(C1C([H])=C([H])C([H])=C([H])C=1[H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])C([H])(C2C([H])=C([H])C(=C([H])C=2[H])C(C(=O)O[H])(C([H])([H])[H])C([H])([H])[H])O[H])C([H])([H])C1([H])[H]
InChi Key	RRJFVPUCXDGFJB-UHFFFAOYSA-N
InChi Code	InChI=1S/C32H39NO4.ClH/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);1H
Chemical Name	2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid;hydrochloride
Synonyms	MDL 16455A; Allegra; Terfenidine carboxylate hydrochloride; Fexofenadine HCl; MDL-16-455A; MDL16455A; MDL 16 455A; Telfast
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Histamine H1 receptor ( IC50 = 246 nM )
ln Vitro	In vitro activity: Fexofenadine has an IC50 value of 95.5 nM and demonstrates a strong, concentration-dependent anti-anaphylactic effect. For the 5-HT2A receptors from the rat caudal artery with a pA2 of 5.2, fexofenadine only exhibits a weak competitive antagonist behavior. On the Papp of fexofenadine in both directions in the Caco-2 cell model, all four P-gp inhibitors exhibit a strong, concentration-dependent effect.[1] On the P-gp-mediated secretion of Fexofenadine, verapamil's half-life (IC50) is 8.44 mM.[2] In the rabbit left ventricular wedge preparation, fed at doses greater than 100 times its free TPC, fedofenadine significantly increases the QT and Tp-e intervals and receives a significant TdP score.[3].
ln Vivo	Fexofenadine exhibits negligible metabolism in rats as evidenced by its unchanged excretion in urine, bile, and the gastrointestinal tract, rendering it a perfect probe for researching transport mechanisms. Coadministration of Fexofenadine with Ketoconazole increases the oral exposure of Fexofenadine by 187% in rats. On the other hand, rats given Fexofenadine in combination with either orange juice or apple juice experience a 31% or 22% reduction in oral exposure to the drug. Fexofenadine oral exposure is further reduced by increasing the amount of orange or apple juice given, by 40% and 28%, respectively.[4] The clearance of Fexofenadine from the biliary system (17 ml/min/kg) in mice makes up nearly 60% of the total clearance (30 ml/min/kg). Knockout mice of Mdr1a/1b P-gp does not affect the biliary excretion clearance with regard to both plasma and liver concentrations, whereas the absence of P-gp causes a 6-fold increase in the plasma concentration and 3-fold higher brain-to-plasma concentration ratio after oral administration.[5]
Cell Assay	Fexofenadine hydrochloride (MDL-16455 hydrochloride) (100 µM; 1 hour) efficiently inhibits phosphorylated p38 activation in histamine-induced nasal fibroblasts.
Animal Protocol	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
References	[1]. Drugs R D . 2005;6(6):371-84. [2]. Pharm Res . 2004 Aug;21(8):1398-404. [3]. Heart Rhythm . 2006 Aug;3(8):948-56.
Additional Infomation	Fexofenadine hydrochloride is a diarylmethane. Fexofenadine Hydrochloride is the hydrochloride salt form of fexofenadine, a carboxylated metabolic derivative of terfenadine and second generation, long-lasting selective histamine H1 receptor antagonist, with antihistaminic activity. Upon administration, fexofenadine competitively binds of peripheral H1-receptors in the gastrointestinal (GI) tract, blood vessels, and bronchial smooth muscle. This prevents binding of histamine to peripheral H1-receptors and prevents their activation. This prevents a histamine-mediated allergic reaction. Fexofenadine does not cross the blood-brain-barrier (BBB). See also: Fexofenadine (has active moiety) ... View More ...

Solubility Data

Solubility (In Vitro)

DMSO: ~107 mg/mL (~198.8 mM) Water: ~2 mg/mL (~3.7 mM) Ethanol: ~107 mg/mL (~198.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.65 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 (4.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8583 mL	9.2916 mL	18.5832 mL
	5 mM	0.3717 mL	1.8583 mL	3.7166 mL
	10 mM	0.1858 mL	0.9292 mL	1.8583 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.