Pharmacokinetics, Safety and Cognitive Function Profile of Rupatadine 10, 20 and 40 mg in Healthy Japanese Subjects: A Randomised Placebo-Controlled Trial.

INTRODUCTION: Rupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses. METHODS: In this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP), reaction time (RT), spatial working memory (SWM) and visual analogue scales (VAS). RESULTS: Exposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10-40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs) or withdrawals due to treatment-emergent adverse events (TEAEs) in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests. CONCLUSIONS: This study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine

A preliminary study on efficacy of rupatadine for the treatment of acute dengue infection

Abstract Currently there are no specific treatments available for acute dengue infection. We considered that rupatadine, a platelet-activating factor receptor inhibitor, might modulate dengue-associated vascular leak. The effects of rupatadine were assessed in vitro, and in a dengue model, which showed that rupatadine significantly reduced endothelial permeability by dengue sera in vitro, and significantly inhibited the increased haematocrit in dengue-infected mice with dose-dependency. We conducted a randomised, placebo-controlled trial in 183 adult patients in Sri Lanka with acute dengue, which showed that rupatadine up to 40 mg daily appeared safe and well-tolerated with similar proportions of adverse events with rupatadine and placebo. Although the primary end-point of a significant reduction in fluid leakage (development of pleural effusions or ascites) was not met, post-hoc analyses revealed small but significant differences in several parameters on individual illness days - higher platelet counts and lower aspartate-aminotransferase levels on day 7 in the rupatadine group compared to the placebo group, and smaller effusions on day 8 in the subgroup of patients with pleural effusions. However, due to the small sample size and range of recruitment time, the potential beneficial effects of rupatadine require further evaluation in large studies focused on recruitment during the early febrile phase