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


CONCLUSIONS
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.
Tashiro
Manabu
M
Division of Cyclotron Nuclear Medicine, Tohoku University, Sendai, Miyagi, Japan. mtashiro@m.tains.tohoku.ac.jp
Kato
Motohisa
M
Miyake
Masayasu
M
Watanuki
Shoichi
S
Funaki
Yoshihito
Y
Ishikawa
Yoichi
Y
Iwata
Ren
R
Yanai
Kazuhiko
K
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002247:Carbon Isotopes / Q000378:metabolism; D017332:Cetirizine / Q000008:administration & dosage* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004316:Doxepin / Q000378:metabolism; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000378:metabolism; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects; D013223:Statistics as Topic; D013997:Time Factors; D055815:Young Adult
D002247:Carbon Isotopes; D006633:Histamine Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D011969:Receptors, Histamine H1; D004316:Doxepin; D006919:Hydroxyzine; D017332:Cetirizine