tacrolimus and azelastine

Allergic eye disease is a term that refers to a number of disease processes that affect about one-fifth of the world's population. Although the more advanced forms of the disease can be sight threatening, the most disabling effects are due to the clinical manifestations, and hence quality of life, with some patients having seasonal exacerbations of their symptoms, whereas others have symptoms that are present throughout the year. Recent increased understanding of the cellular and mediator mechanisms that are involved in the various disease manifestations has greatly facilitated the development of more effective treatment options. Newer topical medications are being used that have multiple actions, such as an antihistaminic effect coupled with mast-cell stabilisation, and which require reduced daily dosing due to their longer duration of action. With greater research into newer therapies and more effective modes of delivery, improved healthcare outcomes with a lower economic burden will be achieved for patients with allergic eye disease.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Cost of Illness; Dibenzoxepins; Drug Administration Schedule; Health Care Costs; Histamine H1 Antagonists; Humans; Immunosuppressive Agents; Mast Cells; Olopatadine Hydrochloride; Phthalazines; Quality of Life; Randomized Controlled Trials as Topic; Tacrolimus; Vision Disorders

Atopic dermatitis is a typical chronic inflammatory skin disease that affects all age groups and requires basic skin care for treatment. Anti-inflammatory and antiallergy steroids are the most frequently used treatments but they are limited due to their side effects caused by a weakening of the immune system. Many consumers focus on performance as a criterion for selecting cosmetics. However, steroids have been illegally used to improve the performance of cosmetics, and consumers have been adversely affected by the corresponding side effects. In this paper, we propose a simple and rapid method using liquid chromatography-tandem mass spectrometry to simultaneously analyze ten non-permitted atopic therapeutic compounds in cosmetic products: chlorpheniramine maleate, ketotifen fumarate, doxepin hydrochloride, azelastine hydrochloride, bufexamac, clotrimazole, tranilast, fusidic acid, tacrolimus, and pimecrolimus. Additionally, the major characteristic fragment ions for tacrolimus, pimecrolimus, and clotrimazole were identified by time-of-flight mass spectrometry. The specificity, linearity, limit of detection, limit of quantification, recovery, precision, accuracy, and stability of the proposed method were validated. The limit of detection and quantification were in the ranges of 5.05-203.30 pg/mL and 15.15-609.90 pg/mL, respectively. The proposed analysis method could help improve the safety management of cosmetics.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Bufexamac; Chlorpheniramine; Chromatography, High Pressure Liquid; Clotrimazole; Cosmetics; Doxepin; Fusidic Acid; Ketotifen; ortho-Aminobenzoates; Phthalazines; Tacrolimus; Tandem Mass Spectrometry

Azelastine hydrochloride (AZE) is an anti-allergic drug that inhibits the release of various chemical mediators from mast cells. We compared the immunosuppressive effects of AZE and FK-506 in vivo and in vitro. Topical application of AZE strongly inhibited the efferent phase of contact hypersensitivity, as did application of FK-506. In in vitro experiments, we found that 1) the suppression by AZE on interleukin (IL)-2 production from splenic T cells was partial and considerably large amounts of IL-2 were still produced, even in the presence of 10(-5) M of AZE, which was in sharp contrast to the observed marked inhibition of [3H]-TdR incorporation; 2) AZE significantly inhibited the phorbol myristate acetate-induced IL-2 responsiveness; 3) AZE did not inhibit the IL-2 receptor alpha expression of activated T cells; and 4) the significant inhibitory action was still observed even when AZE was added at 48 h after the initiation of culture. In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Thus, AZE exerts its in vitro immunosuppressive activity preferentially by interfering with the IL-2 responsiveness, with partial inhibition of IL-2 production. Conversely, FK-506 acts as a strong inhibitor of IL-2 production without a prominent effect on IL-2 responsiveness. The immunosuppressive activity of AZE shown in vitro may also be operative in vivo and may be applicable for topical use.

Topics: Administration, Topical; Animals; Bronchodilator Agents; Cell Division; Cells, Cultured; Dermatitis, Contact; DNA; Immunosuppressive Agents; In Vitro Techniques; Interleukin-2; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Phthalazines; Receptors, Interleukin-2; T-Lymphocytes; Tacrolimus; Tetradecanoylphorbol Acetate; Thymidine; Time Factors; Tritium