Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin.

AIMS: The strength of sedation due to antihistamines can be evaluated using positron emission tomography (PET). The purpose of the present study is to measure histamine H(1) receptor (H(1)R) occupancy following oral administration of cetirizine (10 and 20 mg) in order to examine dose dependency.

METHODS: Fifteen healthy male volunteers (age range, 20-35 years) were divided into 3 subgroups and were studied following single oral administration of cetirizine at 10 mg (n = 5) and 20 mg (n = 5) or hydroxyzine at 30 mg (n = 5) using PET with 11C-doxepin. Each subject was scanned also following the administration of placebo. Binding potential and H(1)RO values were calculated in the prefrontal and anterior cingulate cortices. Subjective sleepiness was also measured, and the correlation to H(1)RO was examined for each antihistamine.

RESULTS: The averaged H(1)ROs of cetirizine 10 mg, 20 mg, and hydroxyzine 30 mg in the prefrontal and cingulate cortices was 12.6%, 25.2%, and 67.6%, respectively. The H(1)RO of hydroxyzine 30 mg correlated well with subjective sleepiness (p < 0.001); however, those of cetirizine 10 and 20 mg showed no correlation with subjective sleepiness.

CONCLUSION: It was demonstrated that the brain penetration of orally administered cetirizine was dose-dependent. Cetirizine 10 mg, with its low H(1)RO and thus minimal sedation, could be more safely used than cetirizine 20 mg for the treatment of various allergic disorders.