Central Effects of Fexofenadine and Cetirizine: Measurement of Psychomotor Performance, Subjective Sleepiness, and Brain Histamine H₁‐Receptor Occupancy Using ¹¹C‐Doxepin Positron Emission Tomography

Abstract

Histamine H1-receptor (H1R) antagonists, or antihistamines, often induce sedative side effects when used for the treatment of allergic disorders. This study compared the sedative profiles of the second-generation antihistamines, fexofenadine and cetirizine, using 3 different criteria: subjective sleepiness evaluated by the Stanford Sleepiness Scale, objective psychomotor tests (simple and choice reaction time tests and visual discrimination tests at 4 different exposure durations), and measurement of histamine H1-receptor occupancy (H1RO) in the brain. Subjective sleepiness and psychomotor performance were measured in 20 healthy Japanese volunteers at baseline and 90 min after administration of fexofenadine 120 mg or cetirizine 20 mg in a double-blind, placebo-controlled crossover study. Hydroxyzine 30 mg was included as a positive control. H1RO was measured using positron emission tomography (PET) with (11)C-doxepin in 12 of the 20 subjects, and a further 11 volunteers were recruited to act as controls. In psychomotor tests, fexofenadine was not significantly different from placebo and significantly less impairing than cetirizine on some tasks, as well as significantly less impairing than hydroxyzine on all tasks. For subjective sleepiness, fexofenadine was not significantly different from placebo, whereas cetirizine showed a trend toward increased sleepiness compared with fexofenadine and placebo. H1RO was negligible with fexofenadine (-0.1%) but moderately high with cetirizine (26.0%). In conclusion, fexofenadine 120 mg is distinguishable from cetirizine 20 mg, as assessed by H1RO and psychomotor testing.

Allergic rhinitis-induced nasal congestion: its impact on sleep quality

“…46,[49][50][51][52] The significant sedation associated with first-generation and certain secondgeneration antihistamines is attributed to their high liposolubility and low molecular weight -which allows penetration into the CNS -and their high affinity for CNS histamine H 1 receptors. 42,[49][50][51][52][53] Most newer second-generation antihistamines have minimal or no sedating properties (due to minimal CNS penetration and a low affinity for central H 1 receptors) and less anticholinergic effects and are therefore preferable to first-generation antihistamines in most cases. [46][47][48][49] The second-generation antihistamine, cetirizine, however, does penetrate the CNS and occupy central H 1 receptors to some extent, resulting in increased sedation compared with fexofenadine.…”

“…[46][47][48][49] The second-generation antihistamine, cetirizine, however, does penetrate the CNS and occupy central H 1 receptors to some extent, resulting in increased sedation compared with fexofenadine. 42,53,54 Azelastine, an intranasal antihistamine with anti-inflammatory properties, has reduced nasal congestion and improved subjective sleep quality in small studies, but was also found to cause somnolence. 55,56 Decongestants are sympathomimetic drugs that constrict capacitance vessels in the turbinates and decrease nasal congestion.…”

New Original Antihistamine Bilastine in the Treatment of Allergic Rhinitis

“…Для него характерны низкий потенциал к лекарственным взаимодействиям, отсутствие способности потенцировать влияние алкоголя на ЦНС и потребности в коррекции дозы при нарушениях функции почек и/или печени. Данные качества позволяют считать препарат Никсар ® одним из лидеров среди Н 1 -антигистаминных препаратов второго поколения [16].…”

Pharmacology of Antihistamines

“…It also became apparent that antihistamines differ in their substrate specificity for P-glycoprotein, fexofenadine being a particularly good substrate[52]. In the brain, the H 1 -receptor occupancy of fexofenadine assessed using positron emission tomography scanning is negligible, <0.1%, and, in psychomotor tests, fexofenadine is not significantly different from placebo[53]. Furthermore, fexofenadine has been shown to be devoid of central nervous effects even at supraclinical doses, up to 360 mg[54].…”