Dose dependency of brain histamine H1 receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [ 11C]doxepin

Manabu Tashiro, Motohisa Kato, Masayasu Miyake, Shoichi Watanuki, Yoshihito Funaki, Yoichi Ishikawa, Ren Iwata, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

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 H1 receptor (H1R) 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 PETwith 11C-doxepin. Each subject was scanned also following the administration of placebo. Binding potential and H 1RO values were calculated in the prefrontal and anterior cingulate cortices. Subjective sleepiness was also measured, and the correlation to H 1RO was examined for each antihistamine. Results: The averaged H 1ROs 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 H1RO 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 H1RO and thus minimal sedation, could be more safely used than cetirizine 20 mg for the treatment of various allergic disorders.

Original languageEnglish
Pages (from-to)540-548
Number of pages9
JournalHuman Psychopharmacology
Volume24
Issue number7
DOIs
Publication statusPublished - 2009

Keywords

  • Binding potential
  • Cetirizine
  • Histamine H receptor (HR)
  • Histamine H receptor occupancy (HRO)
  • Hydroxyzine
  • Positron emission tomography (PET)
  • Sedation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Dose dependency of brain histamine H1 receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [ <sup>11</sup>C]doxepin'. Together they form a unique fingerprint.

Cite this