ZOLPIDEM 10 MG GIVEN AT DAYTIME IS NOT ANTAGONIZED BY 300 MG CAFFEINEIN MAN

Objective: Caffeine counteracts various effects of traditional benzodi azepines (BZDs). As zolpidem, a short-acting hypnotic, is an atypical GABA(A)-BZD agonist, we investigated when caffeine would counteract th e effects of zolpidem as well. Methods: In daytime study I, zolpidem 1 0 mg (capsule) and caffeine 150 or 300 mg (in decaffeinated coffee) we re given, alone and in combinations, to parallel groups (n = 15-17) of healthy students in double-blind and placebo-controlled manner. Objec tive and subjective tests were done before and 45 min and 90 min after intake. Ranked Delta values (changes from baseline) were analysed by one-way contrast ANOVA and Scheffe's tests. In daytime study II, four healthy subjects took zolpidem 10 mg alone, and together with blinded caffeine 250 mg or (at -45 min) erythromycin 750 mg. Objective and sub jective effects were measured and plasma zolpidem concentrations assay ed at baseline and 45 min and 90 min after zolpidem intake. Results: I n study I, practice effects after placebo (ad + 30%) were seen for let ter cancellation and digit symbol substitution but not for flicker fus ion tests. Zolpidem alone significantly impaired (P < 0.05 vs Delta-pl acebo) letter cancellation and digit symbol substitution at 45 min and 90 min, lowered the flicker fusion threshold at 45 min, and caused su bjective drowsiness, mental slowness, clumsiness and feeling of poor p erformance. Caffeine alone showed a non-significant trend to improve o bjective performance. The combined effects of zolpidem and either dose of caffeine matched those measured after zolpidem alone. Zolpidem + c affeine 300 mg was not stronger than zolpidem + caffeine 150 mg in imp airing immediate memory and causing subjective sedation. In study II, zolpidem caused objective and subjective sedation; neither caffeine no r erythromycin modulated the effects of zolpidem or plasma zolpidem co ncentrations. Conclusion: The sedative effects of 10 mg of zolpidem ar e not antagonized by 150-300 mg of caffeine in pharmacodynamic or phar macokinetic terms.