Time effects of food intake on the pharmacokinetics and pharmacodynamics of quazepam.
OBJECTIVE
There is little information on interaction between food and the hypnotic agent quazepam. We therefore studied the effects of food and its time interval on the pharmacokinetics and pharmacodynamics of quazepam.


METHODS
A randomized three-phase crossover study with 2-week intervals was conducted. Nine healthy male volunteers took a single oral 20 mg dose of quazepam under the following conditions: 1) after fasting overnight; 2) 30 min after eating standard meal; or 3) 3 h after eating the same meal. Plasma concentrations of quazepam and its metabolite, 2-oxoquazepam and psychomotor function using the Digit Symbol Substitute Test (DSST), Stanford Sleepiness Scale (SSS) and Visual Analogue Scale were measured up to 48 h.


RESULTS
During the food treatments at 30 min and 3 h before dosing, the peak concentrations (Cmax) were 300% (95% CI 260, 340%; P < 0.001) and 250% (95% CI 210, 290%; P < 0.01) of the corresponding value during the fasting phase. For quazepam, the area under the plasma concentration-time curve from 0 to 8 h measured at 30 min and 3 h before dosing was significantly increased, with the food treatments by 2.4-fold (95% CI 2.0; 2.8-fold; P < 0.001) and 2.1-fold (95% CI 1.7; 2.4-fold; P < 0.01), respectively. In response to pharmacokinetic changes, some of the pharmacodynamics (DSST, P < 0.05; SSS, P < 0.05) differed significantly between fasted status and fed status. No difference was found in any pharmacokinetic or pharmacodynamic parameters between the two food treatment phases.


CONCLUSIONS
A food effect on quazepam absorption is evident and continues at least until 3 h after food intake. The dosing of quazepam after a long period of ordinary fasting might reduce its efficacy because a 3 h interval between the timing of the evening meal and bedtime administration of hypnotics is regarded as normal in daily life.
Yasui-Furukori
Norio
N
Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan. yasufuru@cc.hirosaki-u.ac.jp
Takahata
Takenori
T
Kondo
Tsuyoshi
T
Mihara
Kazuo
K
Kaneko
Sunao
S
Tateishi
Tomonori
T
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001569:Benzodiazepines; D018592:Cross-Over Studies; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D005221:Fatigue / Q000139:chemically induced; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D013850:Thinking / Q000187:drug effects; D013997:Time Factors
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C025130:quazepam