title: Different effects of light food on pharmacokinetics and pharmacodynamics of three benzodiazepines, quazepam, nitrazepam and diazepam.
abstract: OBJECTIVE
  Quazepam, nitrazepam and diazepam are administered under fed or fasted conditions for insomnia or anxiety disorder. Light bedtime food may have clinically relevant effects on the plasma levels of those drugs and hence on psychomotor performance. This study assessed the effect of light food on the pharmacokinetics and pharmacodynamics of these drugs.
  
  
  METHODS
  Twenty-one eligible subjects were randomized to one of three groups of seven subjects: quazepam 20 mg, diazepam 5 mg or nitrazepam 5 mg. Each healthy subject took a single oral dose of the assigned drug after overnight fasting and after light food, on a separate occasion. Blood samples were collected until 72 h after dosing. The plasma samples were assayed using high-pressure liquid chromatography with spectrophotometric detection. Reaction time, critical flicker fusion test and visual analogue scales were conducted.
  
  
  RESULTS
  The peak plasma concentration (C(max)) and area under the concentration-time curve (AUC) of quazepam with light food were 1.2-fold [90% confidence interval (CI): 1.1-1.5; P < 0.05] and 1.5-fold (90% CI: 1.3-1.9; P < 0.05) higher than that without light food, respectively. For nitrazepam and diazepam, the time to peak was delayed about 1 h in fed condition (P > 0.05). However it had no effect on their C(max) and AUC. Reaction time of quazepam with light food was prolonged at 4 and 6 h after dosing and its area under the effect-time curve from 0 to 10 h was increased (P < 0.05).
  
  
  CONCLUSIONS
  Light food increased the bioavailability of quazepam and affected psychomotor performance. Light food delayed T(max) of nitrazepam and diazepam but had no effect on C(max) and AUC.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University Graduate School of Medicinal graduate course, Kanagawa, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yamazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kumagai
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: T
authors.initials: T
authors.lastname: Hasunuma
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Otani
authors.forename: M
authors.initials: M
authors.lastname: Majima
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001569:Benzodiazepines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D018592:Cross-Over Studies; D003975:Diazepam / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018565:Food-Drug Interactions; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D009567:Nitrazepam / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D009567:Nitrazepam; C025130:quazepam; D003975:Diazepam