Bilastine vs. hydroxyzine : occupation of brain histamine H-receptors evaluated by positron emission tomography in healthy volunteers
Farre, Magi (Institut Hospital del Mar d'Investigacions Mèdiques)
Pérez-Mañá, Clara (Institut Hospital del Mar d'Investigacions Mèdiques)
Papaseit, Esther (Institut Hospital del Mar d'Investigacions Mèdiques)
Menoyo, Esther (Institut Hospital del Mar d'Investigacions Mèdiques)
Pérez, Marta (Institut Hospital del Mar d'Investigacions Mèdiques)
Martin, Soraya (Institut Hospital del Mar d'Investigacions Mèdiques)
Bullich, Santiago (Molecular Imaging Centre, CRC Corporación)
Rojas, Santiago (Molecular Imaging Centre, CRC Corporación)
Herance, José Raul (Molecular Imaging Centre, CRC Corporación)
Trampal, Carlos (Molecular Imaging Centre, CRC Corporación)
Labeaga, Luis (FAES FARMA S.A)
Valiente, Román (FAES FARMA S.A)
Universitat Autònoma de Barcelona

Fecha:	2014
Resumen:	A close correlation exists between positron emission tomography (PET)-determined histamine H-receptor occupancy (HRO) and the incidence of sedation. Antihistamines with HRO <20% are classified as non-sedating. The objective was to compare the HRO of bilastine, a second generation antihistamine, with that of hydroxyzine. This randomized, double-blind, crossover study used PET imaging with [ 11 C]-doxepin to evaluate HRO in 12 healthy males (mean age 26. 2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and HROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated. The mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0. 26 vs. 0. 13, P < 0. 01; mean difference and 95% CI −0. 130 [−0. 155, 0. 105]). There was no significant difference between bilastine and placebo. Overall HRO by bilastine was significantly lower than that by hydroxyzine (mean value −3. 92% vs. 53. 95%, P < 0. 01; mean difference and 95% CI 57. 870% [42. 664%, 73. 075%]). There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine. A single oral dose of bilastine 20 mg had minimal HRO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Antihistamines H-1 ; Bilastine ; Histamine H-1-receptor occupancy ; Positron emission tomography ; PET
Publicado en:	British Journal of Clinical Pharmacology, Vol. 78 (october 2014) , p. 970-980, ISSN 1365-2125

DOI: 10.1111/bcp.12421
PMID: 24833043

11 p, 1.6 MB

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