Brain histamine H1 receptor occupancy of loratadine measured by positron emission topography: comparison of H1 receptor occupancy and proportional impairment ratio

Aims We have evaluated the sedative properties of H1-antihistamines by using positron emission tomography (PET) and (11)C-doxepin. The purpose of the present study was to measure histamine H1 receptor occupancy (H1RO) of loratadine 10 mg in patients with allergic rhinitis and to compare this occupancy with that of d-chlorpheniramine 2 mg, a first-generation antihistamine. We also compared our PET findings with the proportional impairment ratio reported by McDonald et al. Methods The H1RO of loratadine 10 mg and d-chlorpheniramine 2mg were evaluated in human brains in a double-blind and crossover design using (11)C-doxepin PET. Eleven young male patients with allergic rhinitis were examined by PET following oral single administration of loratadine 10 mg and d-chlorpheniramine 2 mg. Results Loratadine 10 mg occupied 11.7 +/- 19.5% of histamine H1 receptors in the cortex, whereas d-chlorpheniramine 2mg occupied 53.0 +/- 33.2% in the same area, suggesting a non-sedating property of loratadine at a dose of 10mg. The H1RO values of loratadine and d-chlorpheniramine as well as those of previous studies were found to be significantly proportional to the proportional impairment ratio (r = 0.899). Conclusion Measurement of H1RO is a sensitive and absolute method to characterize the non-sedating property of drugs with H1 antagonistic activity. Copyright (C) 2011 John Wiley & Sons, Ltd.