Lodoxamide

Absorption

In a study of twelve healthy adult volunteers, topical administration of lodoxamide tromethamine ophthalmic solution 0.1%, one drop in each eye four times per day for ten days, did not result in any measurable lodoxamide plasma levels at a detection limit of 2.5 ng/mL.

Description

Trometamol (2-amino-2-(hydroxymethyl)-1,3- propanediol) salt . Lodoxamide is an antiallergic drug acting as a mast-cell stabilizer, which is effective in the treatment of allergic conjunctivitis .

Originator

Lodoxamide,Alcon,USA

The Uses of Lodoxamide

Lodoxamide is an antiallergic drug that acts as a mast cell stabilizer. It is effective in the treatment of allergic conjunctivitis and in decreasing vascular permeability.

The Uses of Lodoxamide

Harmful

Background

Lodoxamide is a mast-cell stabilizer for topical administration into the eye. Mast-cell stabilizers, first one approved being cromolyn sodium, are used in treatment of ocular hypersensitivity reactions such as vernal conjunctivitis. These conditions often require treatment with anti-inflammatory medications such as ophthalmic NSAIDs or topical steroids which may cause systemic or toxic effects long-term. Although less effective than topical steroids at decreasing inflammation, mast-cell stabilizers offer another treatment option and exhibit minimal adverse effects. Lodoxamide is marketed under the brand name Alomide by Alcon.

Indications

Indicated in the treatment of the ocular disorders referred to by the terms vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis.

Definition

ChEBI: Lodoxamide is an organooxygen compound and an organonitrogen compound. It is functionally related to an alpha-amino acid.

Manufacturing Process

To a solution of 1.56 mole of stannous chloride dihydrate in 860 ml of concentrated hydrochloric acid is added 0.2195 mole of 4-chloro-3,5- dinitrobenzonitrile. The mixture is stirred at room temperature for 2 hours and cooled to 0°C in an ice-salt bath. A cold solution of 50% sodium hydroxide is added to the mixture until strongly basic. During the addition the temperature is kept below 30°C.The precipitate is removed by filtration and extracted three times with 400 ml of ethyl acetate. The extracts are combined and added to the aqueous filtrate. The phases are shaken well for ten minutes and separated. The organic phase is evaporated to dryness in vacuo. The solid residue is recrystallized from ethanol-water. There is obtained 25.0 g (68%) of 4-chloro-3,5-diaminobenzonitrile, melting point 169-170°C.
To a solution of 0.34 mole of 4-chloro-3,5-diaminobenzonitrile in 160 ml of dry DMF is added 0.82 mole of triethylamine. The solution is cooled to 5°C andthere is added 0.82 mole of ethyloxalyl chloride dropwise, keeping the temperature less than 15°C. The mixture is stirred for 1 hour and warmed to room temperature. The mixture is stirred at room temperature for 24 hours. The precipitate is removed by filtration and washed two times with ethyl acetate. The filtrate and washes are combined and the ethyl acetate distilled off in vacuo. The DMF solution is poured into 3 L of water. The semi-solid residue is removed by filtration. The residue is recrystallized from ethanol. There is obtained 72.4 g (58%) of diethyl N,N'-(2-chloro-5-cyano-mphenylene)dioxamate, melting point 177-179°C.
A solution of 0.197 mole of diethyl (N,N'-(2-chloro-5-cyano-m-phenylene) dioxamate in 750 ml of methylene chloride is extracted with 465 ml of 1 N sodium hydroxide. The aqueous phase is separated and stirred for 20 min at room temperature. The solution is acidified with dilute hydrochloric acid. The precipitate is removed by filtration and washed with water. There is obtained 59.1 g (96%) of N,N'-(2-chloro-5-cyano-m-phenylene)dioxamic acid, melting point 212°C (dec.).

brand name

Alomide (Alcon).

Therapeutic Function

Anti-asthmatic, Antiallergic

Biochem/physiol Actions

Lodoxamide Tromethamine is a potent agonist of GPR35 in both human and rat, and an antiallergic mast cell stabilizer used clinically in the UK for treatment of allergic conjunctivitis.

Pharmacokinetics

Lodoxamide is a mast cell stabilizer that inhibits the in vivo Type 1 immediate hypersensitivity reaction. Lodoxamide therapy inhibits the increases in cutaneous vascular permeability that are associated with reagin or IgE and antigen-mediated reactions.

Metabolism

Not Available