The effects of acute doses of fexofenadine, promethazine, and placebo on cognitive and psychomotor function in healthy Japanese volunteers.
BACKGROUND
Genetic variations in cross-cultural metabolic capability may attenuate the lack of central nervous system effects of fexofenadine.


OBJECTIVE
To compare the pharmacodynamics of fexofenadine and promethazine versus placebo in Japanese volunteers.


METHODS
In this randomized, crossover, double-blind study, 24 subjects received single doses of fexofenadine 60 mg and 120 mg, promethazine 25 mg, and placebo, with a 6-day washout period between treatments. Objective measures included critical flicker fusion, choice reaction time, and a compensatory tracking task. A line analog rating scale evaluated self-rated sedation. A rapid visual information-processing task evaluated vigilance at baseline and at 2 hours.


RESULTS
Fexofenadine was not significantly different from placebo on any test at any timepoint. In contrast, promethazine impaired critical flicker fusion thresholds (F[3,63] = 5.37, P = 0.0023); increased recognition reaction time (F[3,63] = 13.63, P < 0.0001) and total reaction time (F[3,63] = 12.23, P < 0.0001) components of the choice reaction time test; reduced tracking accuracy (F[3,63] = 14.25, P < 0.0001) and increased reaction times to peripheral stimuli (F[3,63] = 9.29, P < 0.0001) in the compensatory tracking task; reduced the number of valid responses (F[3,63] = 14.86, P < 0.0001) and impaired reaction times (F[3,63] = 12.02, P < 0.0001) in the rapid visual information-processing task test; and impaired subjective ratings of sedation (F[3,63] = 7.55, P = 0.0002), compared with placebo.


CONCLUSIONS
A battery of tests sensitive to impairment by promethazine failed to show any negative cognitive or psychomotor effects with fexofenadine 60 and 120 mg. Fexofenadine is an intrinsically non-impairing antihistamine in Japanese subjects.
Ridout
Fran
F
HPRU Medical Research Centre, University of Surrey, Egerton Road, Guildford, Surrey, United Kingdom. f.ridout@surrey.ac.uk
Hindmarch
Ian
I
D000328:Adult; D044466:Asian People / Q000235:genetics; D001711:Biotransformation / Q000235:genetics; D001812:Blood-Brain Barrier; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011398:Promethazine / Q000493:pharmacokinetics / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D016593:Terfenadine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D016593:Terfenadine; C093230:fexofenadine; D011398:Promethazine