The Effects of Fexofenadine at Steady-State on Sleep Architecture.

Study Objectives: Fexofenadine is a non-sedating, selective histamine H1 receptor antagonist that does not cross the blood--brain barrier. We sought 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 male volunteers using polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT). We evaluated whether a genetic polymorphism of MDR1 could produce variations in pharmacokinetic and pharmacodynamic parameters (PSG) of fexofenadine. Design: A single-site, randomized, double-blind, two-treatment, two-way crossover study of fexofenadine and chlorpheniramine in healthy male volunteers. Setting: Kyungpook National University Hospital, Daegu, Korea. Participants: Ten healthy Korean male volunteers. Interventions: Each subject was randomized to receive one capsule of fexofenadine HCl (Allegra) 180 mg once each morning or chlorpheniramine 6 mg (2 mg in the morning and 4 mg after 12 h) for 3 days. Each treatment period was separated by a washout period of 7 days. Measurements and Results: Each subject underwent overnight PSG on the second night of the treatment period. The MSLT was carried out and the sleep questionnaire was completed the next morning. Blood samples were taken for the assessment of fexofenadine pharmacokinetics and MDR1 genotyping was assessed on the third day. Compared to baseline and fexofenadine, chlorpheniramine significantly increased the latency in rapid eye movement (REM) sleep, but no significant decrease occurred in the percentage of REM sleep. No significant change in latency for REM sleep or %REM sleep after dosing with fexofenadine was observed. Conclusions: Our findings suggest that fexofenadine and chlorpheniramine at steady state have no significant effect on sleep variables, when compared to baseline. The effects of MDR1 genotypes and haplotypes on the pharmacokinetics and pharmacodynamics of fexofenadine were not significant. [ABSTRACT FROM AUTHOR]