Bilastine vs. hydroxyzine: occupation of brain histamine H1 -receptors evaluated by positron emission tomography in healthy volunteers.
OBJECTIVE
A close correlation exists between positron emission tomography (PET)-determined histamine H1 -receptor occupancy (H1 RO) and the incidence of sedation. Antihistamines with H1 RO <20% are classified as non-sedating. The objective was to compare the H1 RO of bilastine, a second generation antihistamine, with that of hydroxyzine.


METHODS
This randomized, double-blind, crossover study used PET imaging with [(11) C]-doxepin to evaluate H1 RO 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 H1 ROs 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.


RESULTS
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 H1 RO 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.


CONCLUSIONS
A single oral dose of bilastine 20 mg had minimal H1 RO, 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.
Human Pharmacology and Neuroscience Research Unit, Hospital del Mar Medical Research Institute-IMIM, and Universidad Autónoma de Barcelona-UAB, Barcelona, Spain.
Magí
M
Farré
Clara
C
Pérez-Mañá
Esther
E
Papaseit
Esther
E
Menoyo
Marta
M
Pérez
Soraya
S
Martin
Santiago
S
Bullich
Santiago
S
Rojas
José-Raúl
JR
Herance
Carlos
C
Trampal
Luis
L
Labeaga
Román
R
Valiente
D000328:Adult; D001334:Automobile Driving / Q000523:psychology; D001562:Benzimidazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D064368:Healthy Volunteers / Q000523:psychology; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D006919:Hydroxyzine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011597:Psychomotor Performance / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000378:metabolism*
D001562:Benzimidazoles; D002250:Carbon Radioisotopes; D006634:Histamine H1 Antagonists; D010880:Piperidines; D011969:Receptors, Histamine H1; D006919:Hydroxyzine; C445659:bilastine
PET; antihistamines H-1; bilastine; histamine H-1-receptor occupancy; positron emission tomography