761 H 1-receptor antagonists: Systemic absorption and peripheral H 1-blockade following administration in topical liposome formulations

Abstract

761 HI-Receptor Antagonists: Systemic Absorption and Peripheral Ht-Blockade Following Administration in Topical Liposome Formulations. KJ Simons PhD, S Venkataram PhD, Y Zheng MSc, FER Simons MD, Winnipeg, Canada. Topical administration of Hrantagonists has the potential to target medication delivery to the skin, with low systemic absorption• We hypothesized that after topical administration in liposome formulations, Hrantagonists would produce greater peripheral Ht-bloekade than after administration in aqueous formulations. We tested this hypothesis in a rabbit model. Cetirizine (C) 10 mg/mL and hydroxyzine (H) 10 mg/mL were prepared in liposome (L) and aqueous (A) formulations. In randomized cross-over studies in rabbits, blood samples were collected and intradermal histamine tests were performed before application of these formulations to the skin (1 mL/20 cm:), and for up to 24 hours afterwards. Serum Ht-antagonist concentrations were measured using HPI.C. Mean wheal areas at each time were compared using the ANOVA and the Tukey and Bonferroni multiple range tests on PC-SAS. Results: CL C_.AA HI., H.AA max serum conct 14+10 8+8 5:!:1 3+2 max % ~ wheal 59+20 59+14 80~11 51~12 serum cone @ 24h? 0 0 0 0 % ~ wheal @ 24h 37:t:9 8±4 39~-14 9+2 t ng/mL; *p<0.05, L vs A Topical application of H:antagonists in liposome formulations resulted in prolonged peripheral H:blockade despite negligible H : antagonist serum concentrations. These liposome formulations might be useful in the treatment of allergic skin disorders. 763 A Doub le -Masked S tudy on the Need fo r Ad junc t ive Steroid T r e a t m e n t in V e r n a l Ke ra tocon junc t i v i t i s Pa t ien ts T r e a t e d wi th Alomide 0 .1% O p h t h a l m i c Solut ion or O p t i c r o m 2 % Authors L Tomazzoli MD .L Seullica MD. C Cesvedns MD. M Irnzubieta, R Sans MD, A Secchi MD Verona Italy, Messina Italy, Barcelona Spain, Sevilla Spain, Madrid Spain, Padova Italy An eight week, randomized, parallel groups study was conducted to compare the need for adjunctive steroid therapy (dexamethasone 0.1%) in patients with vernal keratocoajunctivitis (VKC) treated either with lodoxamide 0.1% (Alomide Alcoa Laboratories), a mast cell stabilizer or with sodium cromoglyeate 2% (Optierem Fisons Pharmaceuticals). Results from 142 patients with moderate to severe vernal keratoconjunetivitis with clinical signs and symptoms showed that Iodoxamide 0.1% ophthalmic solution was clinically and statistically more effective than sodium cromoglycate 2 % in reducing the need for adjunctive steroid use. The average total steroid use in the lodoxamide 0.1% group was 18.3 doses compared with and average of 35.7 doses in the sodium cromoglycate 2% group. The average weekly steroid dose in the Iodoxamide 0.1% group was reduced from approximately 5 doses per week to 0.8 doses per week by Day 35. The sodium cromoglycate 2% weekly dose fell only from an initial 6 doses per week to 4 doses per week by Day 35. These differences were clinically and statistically significant after 2 weeks. Treatment with lodoxamide 0.1% compared to sodium eromoglycate 2% resulted in clinically and statistically lower use of adjunctive steroid therapy required to alleviate signs and symptoms of VKC. Lodoxamide 0.1% was well tolerated by these patients.