INTRODUCTION: The Central Nervous System (CNS) impairment induced by moderate alcohol (ALC) ingestion may be enhanced if other drugs are taken simultaneously. Rupatadine (RUP) is a new H(1)-antihistamine which also inhibits platelet activating factor (PAF) release in inflammatory reactions. OBJECTIVE: The main aim of the study was to assess the effects of ALC 0.8 g/Kg on RUP (10 mg and 20 mg) CNS effects. An evaluation of alcohol and RUP pharmacokinetics was also attained. METHODS: Eighteen healthy young volunteers of both sexes participated in a phase I, randomised, crossover, double-blind, placebo-controlled study. At 2-week intervals they received six treatments: (a) placebo (PLA), (b) ALC alone and ALC in combination with: (c) hydroxyzine 25 mg (HYD), (d) cetirizine 10 mg (CET), (e) RUP 10 mg or (f) RUP 20 mg. At baseline and several times thereafter, seven psychomotor performance tests (finger tapping, fine motoric skills, nystagmus, temporal estimation, critical-flicker-fusion frequency, 'd2' cancellation, simple reaction) and eleven subjective self-reports (drunkenness, sleepiness, alertness, clumsiness, anger, inattentiveness, efficiency, happiness, hostility, interest and extraversion) were carried out. Two-way (treatment, time) ANOVAs for repeated measures to each variable together with a multivariate non-parametric approach were applied. Plasma concentrations of alcohol, and of RUP and its metabolites, were quantified by validated immunofluorescence and LC/MS/MS methods, respectively. Plasma-time curves for all compounds were analysed by means of model-independent methods. RESULTS: The combination of alcohol with HYD, CET and RUP 20 mg produced more cognitive and psychomotor impairment as compared to alcohol alone, being the combination of alcohol and HYD the one which induced the greatest deterioration. The combination of alcohol and RUP 10 mg could not be differentiated from ALC alone. Subjective self-reports reflect effects on metacognition after the combination of alcohol with HYD and CET i.e. the increased objective impairment observed was not subjectively perceived by the subjects. No significant differences were obtained when comparing alcohol plasma concentrations assessed after the treatments evaluated. RUP showed a lineal kinetic relationship after 10 and 20 mg with a higher exposition to both metabolites assayed. CONCLUSIONS: Present results showed that single oral doses of rupatadine 10 mg in combination with alcohol do not produce more cognitive and psychomotor impairment than alcohol alone. Higher doses of rupatadine, in combination with alcohol, may induce cognitive and psychomotor deterioration as hydroxyzine and cetirizine at therapeutic doses.

Analysis of Variance↗

PubMed2006

Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed to aeroallergens in the Vienna Challenge Chamber.

BACKGROUND: Rupatadine is a novel compound with potent dual antihistamine and platelet-activating factor antagonist activities and no sedative effects. OBJECTIVE: To evaluate the efficacy of rupatadine, 10 mg once daily, and placebo on allergen-induced symptoms (including nasal congestion), nasal airflow, nasal secretion, and subjective tolerability in response to grass pollen in a controlled allergen-exposure chamber. METHODS: In a randomized, double-blind, placebo-controlled, crossover trial, 45 patients with a history of seasonal allergic rhinitis received rupatadine or placebo every morning for 8 days in 2 different periods separated by a 14-day washout interval. On day 8 of each crossover period, patients underwent a 6-hour allergen exposure in the Vienna Challenge Chamber, where a constant and homogeneous concentration of aeroallergens was maintained. Subjective and objective assessments were performed online during the exposure. RESULTS: Subjective single and composite nasal and nonnasal symptoms were consistently less severe with rupatadine use than with placebo use starting from the first evaluation at 15 minutes to the end of the 6-hour Vienna Challenge Chamber challenge, with the most significant effects seen for nasal rhinorrhea, nasal itching, sneezing attacks, and total nasal symptoms (P < .001 for all). All the other symptoms (including nasal congestion, P < or = .005) were also significantly reduced with active treatment compared with placebo use. Mean secretion weights and overall feeling of complaint were significantly lower with rupatadine therapy than with placebo use (P < or = .001). Overall, rupatadine treatment was well tolerated. CONCLUSION: Rupatadine treatment is effective and well tolerated in patients with allergen-induced symptoms exposed to aeroallergens in a controlled exposure chamber.

Adolescent↗

PubMed2006

Antithrombotic treatment in atrial fibrillation. Response to: Bereznicki LR, Peterson GM, Jackson SL, Jeffrey EC: the risks of warfarin use in the elderly. Expert Opin. Drug Saf. (2006) 5(3):417-431.

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Acenocoumarol↗

PubMed2004

Central and peripheral evaluation of rupatadine, a new antihistamine/platelet-activating factor antagonist, at different doses in healthy volunteers.

AIMS: To assess peripheral anti-H1 and central nervous system (CNS) activity of single increasing doses of rupatidine fumarate (RU), a new antihistamine/platelet-activating factor antagonist compound, in comparison with hydroxyzine and placebo. METHODS: Eighteen healthy young subjects of both sexes took part in a crossover, randomised, double-blind, placebo-controlled study. Treatments tested were: RU 10, 20, 40 and 80 mg and hydroxyzine 25 mg, as a positive standard. Before and several times after drug intake, peripheral anti-H1 activity was appraised by the skin reactivity to intradermal injection of histamine. CNS effects were also obtained by objective tests of psychomotor performance and subjective mood scales. RESULTS: All active treatments showed a significant reduction of the wheal and flare reaction in relation to placebo, RU displaying a potent dose-dependent inhibition pattern. The global nonparametric Friedman test to changes from placebo in 15 objective variables from psychomotor performance showed a significant impairment of similar magnitude after hydroxyzine 25 mg (p = 0.01) and RU 80 mg (p = 0.02), but this was slower in development and recovery after the latter. After RU 40 mg, a smaller impairment was also obtained (p = 0.04). Activity (p = 0.01) and drowsiness (p = 0.02) scales showed significant changes, the subjects feeling less active and more drowsy after all active treatments. CONCLUSION: RU presents a potent dose-dependent peripheral anti-H1 activity, displaying psychomotor impairment activity only at the highest dose (80 mg), while therapeutically relevant lower doses (10 and 20 mg) were similar to placebo.

Adult↗

PubMed2003

Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis.

Rupatadine is a new agent for the management of diseases with allergic inflammatory conditions, such as seasonal and perennial rhinitis. The pharmacological profile of rupatadine offers particular benefits in terms of a strong antagonist activity towards both histamine H1 receptors and platelet-activating factor (PAF) receptors. Rupatadine has a rapid onset of action, and its long-lasting effect (>24 h) permits once-daily dosing. Rupatadine should not be used in combination with the cytochrome P450 inhibitors, such as erythromycin or ketoconazole, due to an increase in AUC and Cmax for rupatadine, although no clinically relevant adverse events have been reported. In addition, rupatadine, at the recommended dose of 10 mg, has been shown to be free of sedative effects and not to cause significant changes in the corrected QT interval in special populations, including the elderly, nor when coadministered with erythromycin or ketoconazole. Preclinical data have also shown that rupatadine and its main active metabolites did not interfere with cloned human HERG channel and did not affect in vitro isolated dog Purkinje fibers at concentrations at least 2000 times greater than those obtained with therapeutic doses in humans. Rupatadine is clinically effective in relieving symptoms in patients with seasonal and perennial allergic rhinitis. Newly published data on its efficacy and safety suggest that this compound may improve the nasal and non-nasal symptoms in comparison to other currently available second generation H1 receptor antihistamines.

Animals↗

PubMed2002

Economic evaluation of triflusal and aspirin in the treatment of acute myocardial infarction.

OBJECTIVE: To compare the costs to the Spanish healthcare system of 35 days' treatment with triflusal (600 mg/day) and aspirin (300 mg/day) in patients with confirmed acute myocardial infarction within 24 hours of onset of symptoms. DESIGN: A cost minimisation analysis based on the results of the Triflusal in Acute Myocardial Infarction study (TIM) was conducted. The hypothesis was that despite a higher acquisition cost of triflusal, savings would result because of differences in efficacy and safety outcome (non-fatal cerebrovascular event and haemorrhagic events). Diagnostic Related Groups were used as a proxy for determining hospital costs in Spain and the values were obtained from different sources and refer to year 2000 costs. Only direct medical costs were considered for the economic analysis. RESULTS: Although the acquisition cost of triflusal was more expensive than that of aspirin, the cost of prevented events - non-fatal ischaemic cerebrovascular events and cerebral haemorrhages - entirely compensated for the cost of triflusal. The overall cost of treating patients with triflusal, compared with aspirin, represented a net saving of 28.4% per patient treated. CONCLUSION: Our study showed that triflusal is cost saving compared with aspirin in the treatment of the acute phase of myocardial infarction.

Acute Disease↗