Bepotastine salicylate

Objectives: Perennial allergic rhinitis (PAR) is common in Japan. Second-generation antihistamines (SGAs) are commonly used for its treatment; however, it remains unclear which SGA is the most cost-effective. Additionally, the pharmacoeconomics of Japanese Kampo shoseiryuto (which was traditionally prescribed to treat PAR in Japan) remains poorly understood. In this study, we aimed to investigate the effectiveness of various SGAs and shoseiryuto for the treatment of PAR in Japanese outpatients, from the healthcare payer’s perspective. Methods: The most cost- and clinically effective SGAs were determined from a list of 6 SGAs (bepotastine, 10 mg; cetirizine, 10 mg; ebastine, 10 mg; epinastine, 20 mg; loratadine, 10 mg; and olopatadine, 5 mg) together with shoseiryuto, using the overall improvement rate through a model-based analysis. The time horizon was 28 days. Costs were determined based on the Medical Fee Index in 2020. Deterministic and probabilistic sensitivity analyses were conducted to address the uncertainty of the base-case results. Results: Overall, bepotastine (10 mg) and ebastine (10 mg) were cost-effective. Shoseiryuto was less cost-effective than ebastine (10 mg) (dominated). Ebastine (10 mg) was the most cost-effective option based on deterministic and probabilistic sensitivity analyses. Conclusions: Ebastine (10 mg) was the most cost-effective treatment strategy for PAR among the agents evaluated in this study. This insight could aid in establishing an appropriate formulary for treating PAR in hospitals and communities.

Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARβ). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.