Display Settings:

Format

Send to:

Choose Destination
Br J Clin Pharmacol. 2006 Jan;61(1):16-26.

Brain histamine H receptor occupancy of orally administered antihistamines measured by positron emission tomography with (11)C-doxepin in a placebo-controlled crossover study design in healthy subjects: a comparison of olopatadine and ketotifen.

Author information

  • 1Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. mtashiro@mail.tains.tohoku.ac.jp

Abstract

AIMS:

The strength of sedation due to antihistamines can be evaluated by using positron emission tomography (PET). The purpose of the present study is to measure histamine H(1) receptor (H(1)R) occupancy due to olopatadine, a new second-generation antihistamine and to compare it with that of ketotifen.

METHODS:

Eight healthy males (mean age 23.5 years-old) were studied following single oral administration of olopatadine 5 mg or ketotifen 1 mg using PET with (11)C-doxepin in a placebo-controlled crossover study design. Binding potential ratio and H(1)R occupancy were calculated and were compared between olopatadine and ketotifen in the medial prefrontal (MPFC), dorsolateral prefrontal (DLPFC), anterior cingulate (ACC), insular (IC), temporal (TC), parietal (PC), occipital cortices (OC). Plasma drug concentration was measured, and correlation of AUC to H(1)R occupancy was examined.

RESULTS:

H(1)R occupancy after olopatadine treatment was significantly lower than that after ketotifen treatment in the all cortical regions (P < 0.001). Mean H(1)R occupancies for olopatadine and ketotifen were, respectively: MPFC, 16.7 vs. 77.7; DLPFC, 14.1 vs. 85.9; ACC, 14.7 vs. 76.1; IC, 12.8 vs. 69.7; TC, 12.5 vs. 66.5; PC, 13.9 vs. 65.8; and OC, 19.5 vs. 60.6. Overall cortical mean H(1)R occupancy of olopatadine and ketotifen were 15% and 72%, respectively. H(1)R occupancy of both drugs correlated well with their respective drug plasma concentrations (P < 0.001).

CONCLUSION:

It is suggested that 5 mg oral olopatadine, with its low H(1)R occupancy and thus minimal sedation, could safely be used an antiallergic treatment for various allergic disorders. Abbreviations histamine H(1) receptor (H(1)R), histamine H(1) receptor occupancy (H(1)RO), dopamine D(2) receptor (D(2)R), positron emission tomography (PET), blood-brain barrier (BBB), binding potential ratio (BPR), distribution volume (DV).

PMID:
16390347
[PubMed - indexed for MEDLINE]
PMCID:
PMC1884984
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing Icon for PubMed Central
    Loading ...
    Write to the Help Desk