Methods and compositions using terfenadine metabolites in combination with leukotriene inhibitors

Abstract

Methods and pharmaceutical compositions employing a terfenadine metabolite and a leukotriene inhibitor for the treatment or prevention of inflammation or allergic disorders, such as asthma, or symptoms thereof. Also included are methods and compositions employing a terfenadine metabolite, a leukotriene inhibitor, and a decongestant for the treatment or prevention of inflammation or allergic disorders, such as asthma, or symptoms thereof.

Description

1. FIELD OF THE INVENTION[0001] The invention relates to methods of treating asthma, allergic conditions, and inflammation. In another aspect, this invention relates to the use of antihistamines and leukotriene inhibitors, and to compositions containing them.2. BACKGROUND OF THE INVENTION[0002] Terfenadine is an antagonist of the H-1 histamine receptor protein, which mediates the response antagonized by conventional antihistamines. Terfenadine is well absorbed but is extensively metabolized. See Okerholm et al., Biopharmaceutics and Drug Distribution, 2: 185-190 (1981). Two main metabolites have been identified and one of the metabolites, fexofenadine, chemically named 4-[1-hydroxy-4[4-(hydroxydiphenylmethyl-1--piperidinyl)butyl]-.alpha.,.alpha.-dimethylbenzeneacetic acid, is reported to have antihistaminic activity. See Gartiez et al., Arzneimittel Forschung / Drug-Research; 32: 1185-1190 (1982).[0003] Recently, the FDA has approved the use of fexofenadine as a prescription antihista...

AI Technical Summary

Benefits of technology

[0011] The compositions of the invention employing a terfenadine metabolite and a leukotriene inhibitor, and optionally a decongestant, possess potent antihistaminic activity and are useful in treating, preventing, or managing asthma, asthma symptoms, allergic rhinitis, inflammation, and other allergic disorders, as well as dermatitis. The compositions employing a terfenadine metabolite and a leukotriene inhibitor are preferred, and these provide an improvement in overall therapy relative to terfenadine or a terfenadine metabolite alone. In addition, the compositions of the invention reduce or avoid adverse effects associated with administration of other non-sedating antihistamines or derivatives thereof, such as terfenadine, including, but not limited to, cardiac arrhythmias, drowsiness, nausea, fatigue, weakness and headache. The compositions of a terfenadine metabolite and a leukotriene inhibitor are also useful in combination with non-steroidal anti-inflammatory agents or other non-narcotic analgesics for the treatment or prevention of cough, cold, cold-like, and / or flu symptoms and the discomfort, headache, pain, fever, and general malaise associated therewith. The aforementioned combinations (e.g., a terfenadine metabolite and a leukotriene inhibitor) may optionally include one or more other active components including a decongestant, cough suppressant / antitussive, or expectorant.

Problems solved by technology

The study further mentioned a possible mechanism for loratadine and terfenadine, but concluded that the mechanism does not appear to warrant great attention for drug development.

Compounds within the class of non-sedating antihistamines have been known to cause severe adverse electrophysiologic side-effects when administered to a human.

In some patients, zileuton was reported to cause headache, pain, asthenia, dyspepsia, nausea, and myalgia.