Article

Comparison of Peripheral and Central Effects of Single and Repeated Oral Dose Administrations of Bilastine, a New H-1 Antihistamine A Dose-Range Study in Healthy Volunteers With Hydroxyzine and Placebo as Control Treatments

Centre d'Investigació de Medicaments, Institut de Recerca, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Journal of clinical psychopharmacology (Impact Factor: 3.76). 12/2008; 28(6):675-85. DOI: 10.1097/JCP.0b013e31818b2091
Source: PubMed

ABSTRACT Peripheral anti-H1 and central nervous system (CNS) activities after single (day 1) and repeated (day 7) administrations of increasing doses of bilastine (BIL) were assessed in 20 healthy volunteers throughout a crossover, randomized, double-blind, placebo (PLA)-controlled study. Repeated doses of BIL 20, 40, or 80 mg and hydroxyzine 25 mg (HYD) as positive standard were administered on 7 consecutive days. Before and at several time points after drug intake, skin reactivity to the intradermal injection of histamine, objective tests of psychomotor performance, and subjective mood scales were evaluated. All active treatments led to a significant and similar reduction in the wheal reaction in relation to PLA after both the single (P < 0.001) and repeated administrations (P < 0.001). No delay was observed in the onset of its peripheral activity after the first dose of BIL as compared with HYD. No tolerance or sensitization was seen when comparing acute and repetitive assessments. Central nervous system effects showed that HYD induced the greatest psychomotor impairment (P < 0.05). Repeated HYD intake showed a lower number of significant alterations in comparison to acute administration. Bilastine 80 mg also showed some impairment (P < 0.05). Subjectively, the only active treatment that could not be differentiated from PLA was BIL 20 mg. Hydroxyzine 25 mg showed the greatest differentiation (P < 0.01). A clear dissociation between peripheral anti-H1 and CNS activity was found after BIL treatment. Significant and sustained peripheral H1-blocking effects were observed after both single and repeated administrations of the therapeutic dose of 20 mg BIL. The 40-mg dose of BIL produced subjective report of sedation, whereas unwanted objective CNS side effects were observed only with the 80-mg dose.

1 Follower
 · 
94 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The UV polymerization of perfluorinated acrylic polymer for optical waveguide was studied by FTIR spectroscopy. 15 μm of ZPU12-450 and 6 μm of ZPU12-456 required 8 and 3 minutes repectively to be fully UV cured with low intensity of 14 mW/cm<sup>-2</sup> at room temperature in the presence of nitrogen flowing. These results showed that delay of curing reaction with increasing depth in the coating. Besides, UV induced polymerization is found faster than thermal curing reaction.
    Semiconductor Electronics, 2004. ICSE 2004. IEEE International Conference on; 01/2005
  • [Show abstract] [Hide abstract]
    ABSTRACT: Whilst pharmacokinetics describe the relationship between dose levels and concentration-time profiles of a drug in the body and pharmacodynamics describe the concentration-response relationships, pharmacokinectics-pharmacodynamics(PK-PD) models link these two items providing a framework for modelling the time course of drug response. In this chapter, PK-PD models, describing the therapeutic effects of drugs used for the therapy of allergic diseases have been reviewed. Emphasis was given also to the description of the receptor occupancy, which is tightly related to the downstream clinical response. PK - PD models describing unwanted effects were also commented. An integrated use of these models allows choosing appropriate dosing regimens and providing an objective evaluation of the benefit/risk balance.
    Drug Metabolism Reviews 02/2009; 41(3):455-74. DOI:10.1080/10837450902891535 · 6.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bilastine is a new non-sedative H(1) receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial). To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR). Overall, 683 SAR patients, aged 12-70 years, were randomized to a double-blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non-nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre-determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS-AUC(0-14 days)). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms. The mean TSS-AUC(0-14 days) (score x day) was reduced in bilastine- and cetirizine-treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P<0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine-treated group experienced somnolence (1.8%; P<0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine-treated group (7.5% and 4.8%, respectively). Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.
    Clinical & Experimental Allergy 04/2009; 39(9):1338-47. DOI:10.1111/j.1365-2222.2009.03257.x · 4.32 Impact Factor
Show more