title: Zolpidem 10 mg given at daytime is not antagonized by 300 mg caffeine in man.
abstract: OBJECTIVE
  Caffeine counteracts various effects of traditional benzodiazepines (BZDs). As zolpidem, a short-acting hypnotic, is an atypical GABAA-BZD agonist, we investigated when caffeine would counteract the effects of zolpidem as well.
  
  
  METHODS
  In daytime study I, zolpidem 10 mg (capsule) and caffeine 150 or 300 mg (in decaffeinated coffee) were given, alone and in combinations, to parallel groups (n = 15-17) of healthy students in double-blind and placebo-controlled manner. Objective 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 subjective effects were measured and plasma zolpidem concentrations assayed at baseline and 45 min and 90 min after zolpidem intake.
  
  
  RESULTS
  In study I, practice effects after placebo (ad + 30%) were seen for letter cancellation and digit symbol substitution but not for flicker fusion tests. Zolpidem alone significantly impaired (P < 0.05 vs delta placebo) letter cancellation and digit symbol substitution at 45 min and 90 min, lowered the flicker fusion threshold at 45 min, and caused subjective drowsiness, mental slowness, clumsiness and feeling of poor performance. Caffeine alone showed a non-significant trend to improve objective performance. The combined effects of zolpidem and either dose of caffeine matched those measured after zolpidem alone. Zolpidem + caffeine 300 mg was not stronger than zolpidem + caffeine 150 mg in impairing immediate memory and causing subjective sedation. In study II, zolpidem caused objective and subjective sedation; neither caffeine nor erythromycin modulated the effects of zolpidem or plasma zolpidem concentrations.
  
  
  CONCLUSIONS
  The sedative effects of 10 mg of zolpidem are not antagonized by 150-300 mg of caffeine in pharmacodynamic or pharmacokinetic terms.
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Helsinki, Finland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mattila
authors.forename: M L
authors.initials: ML
authors.lastname: Nurminen
authors.forename: P
authors.initials: P
authors.lastname: Vainio
authors.forename: J
authors.initials: J
authors.lastname: Vanakoski
mesh_terms: D000328:Adult; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors*; D008297:Male; D010919:Placebos; D011725:Pyridines / Q000037:antagonists & inhibitors*; D000077334:Zolpidem
chemical_list: D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D010919:Placebos; D011725:Pyridines; D002110:Caffeine; D000077334:Zolpidem