A comparison of olopatadine 0.2% ophthalmic solution versus fluticasone furoate nasal spray for the treatment of allergic conjunctivitis.

Allergic conjunctivitis is an inflammatory condition of the ocular surface characterized by ocular itching, redness, tearing, chemosis, and eyelid swelling. The purpose of this study was to assess the comparative efficacy of an ophthalmic antihistamine/mast cell stabilizer solution and an intranasal steroid at reducing the signs and symptoms of allergic conjunctivitis induced by the conjunctival allergen challenge (CAC) model. Sixty subjects were enrolled in a single center, randomized, placebo-controlled, parallel-treatment, four-visit CAC study. After titration and confirmation of the allergic reaction at visits 1 and 2, subjects were randomized at visit 3 into one of 4 treatment groups (olopatadine 0.2% ophthalmic solution, fluticasone furoate nasal spray, a tear substitute, or saline nasal spray), dosed with study medication, and challenged 15 minutes later, after which ocular allergic signs and symptoms were assessed. Subjects continued treatment of the assigned medication for 6 days. At visit 4, subjects underwent similar procedures to those performed at visit 3. Fifty-nine subjects completed the study. Olopatadine 0.2% ophthalmic solution showed statistical and clinical superiority over fluticasone furoate nasal spray at all post-CAC time points after a single dose (p < 0.001) and after a 1-week loading period (p < 0.01) for ocular itching, the primary end point. Similarly, olopatadine 0.2% showed statistical and clinical superiority over fluticasone furoate for the majority of time points for ocular redness, tearing, chemosis, and eyelid swelling. Olopatadine 0.2% ophthalmic solution was statistically and clinically superior to fluticasone furoate nasal spray for the relief of signs and symptoms of allergic conjunctivitis.

Enhancement of basophil apoptosis by olopatadine and theophylline.

Regulation of basophil survival is an important aspect in the pathogenesis of allergic inflammation associated with local accumulation of basophils. However, pharmacologic modulation of basophil survival is largely unknown except for the apoptosis-enhancing effect of glucocorticoids. We tested the effects of two anti-allergic and anti-asthmatic drugs, olopatadine and theophylline, on basophil survival. Basophils were highly purified from normal human peripheral blood. Apoptosis was analyzed by flow cytometry using annexin V staining or another staining method that detected alterations in the mitochondrial transmembrane potential. In addition to the conventional method using annexin V, basophil apoptosis was successfully established by analysis of the mitochondrial transmembrane potential. Olopatadine decreased the number of live basophils, and they induced apoptosis of basophils during culture. The decline in live basophils was induced by olopatadine even when low doses of IL-3 were included in the culture medium. Theophylline also affected basophil apoptosis and induced a decrease in the number of live basophils. Basophil apoptosis was enhanced by both olopatadine and theophylline. This effect may partly explain the pharmacologic basis of why these drugs are effective on allergic diseases.

Synthesis of a dibenz[b,e]oxepin-bovine serum albumin conjugate for radioimmunoassay of KW-4679 ((Z)-11-[3-(dimethylamino)propylidene]-6,11- dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride).

(Z)-11-[3-(Dimethylamino)propylidene]-2-(methoxycarbonyl)methyl-6, 11- dihydrodibenz[b,e]oxepin-9-acrylic acid (5) was prepared for application to the radioimmunoassay of KW-4679 (1, (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e ] oxepin-2-acetic acid hydrochloride). The acrylic acid moiety in the 9-position of 5 was employed for coupling with an amino group of bovine serum albumin (BSA) to provide 17. Subsequently, the conjugate 17 was treated with aqueous NaOH to hydrolyze the terminal methoxycarbonyl group in the 2-position of the BSA conjugated 5. Antiserum raised against the antigenic BSA-conjugate 4 finally obtained was specific for 1.