The effects of fexofenadine at steady-state on sleep architecture: a study using polysomnography in healthy Korean volunteers.
OBJECTIVE
To compare the effects of a first-generation antihistamine, chlorpheniramine, with those of the second-generation antihistamine, fexofenadine, at steady-state, on nocturnal sleep architecture in healthy Korean volunteers using polysomnography and the Multiple Sleep Latency Test. We evaluated whether a genetic polymorphism of multi-drug resistance 1 gene (MDR1) could produce variations in pharmacokinetic and pharmacodynamic parameters of fexofenadine.


METHODS
Ten healthy male volunteers received one capsule of fexofenadine 180 mg once each morning or chlorpheniramine 6 mg (2 mg in the morning and 4 mg after 12 h) for 3 days, in a single-site, randomized, double-blind, two-treatment, multiple-dosing, two-way crossover study, with a washout period of 7 days. Overnight polysomnography was measured on the second night of the treatment period. The Multiple Sleep Latency Test was carried out the next morning. Blood samples were taken for the assessment of fexofenadine pharmacokinetics and MDR1 genotyping on the third day.


RESULTS
Compared with baseline and fexofenadine, chlorpheniramine significantly increased the latency in rapid eye movement (REM) sleep, with no significant decrease in the percentage of REM sleep. No significant change in latency for REM sleep or percentage REM sleep after dosing with fexofenadine was observed. There was no significant change in the daytime sleepiness with fexofenadine and chlorpheniramine. The effects of MDR1 genotypes and haplotypes on the pharmacokinetics and pharmacodynamics of fexofenadine were not significant.


CONCLUSIONS
Our findings suggest that fexofenadine and chlorpheniramine at steady-state have no significant effect on nocturnal sleep variables and daytime sleepiness, when compared to baseline.
Lee
Ho-Won
HW
Kyungpook National University Hospital, Department of Neurology, 50 Samduk-dong 2 Ga, Jung-gu, Daegu, 700-721, Korea.
Lee
Hae Won
HW
Park
Dae Jin
DJ
Moon
Sung Ok
SO
Ahn
Ju Hee
JH
Kim
Mi Jin
MJ
Kim
Sung-Doo
SD
Kim
Ji-Eun
JE
Yoon
Young-Ran
YR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D019540:Area Under Curve; D002744:Chlorpheniramine / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005838:Genotype; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007723:Korea; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D016593:Terfenadine; C093230:fexofenadine