Document Detail

Effect of dietary fat content in meals on pharmacokinetics of quazepam.
MedLine Citation:
PMID:  12463728     Owner:  NLM     Status:  MEDLINE    
Dietary fat content in meals has been reported to increase the absorption of several drugs proportionately. However, there is no information about the effects of dietary fat in meals on the sedative hypnotic agent quazepam, although limited data suggest that food intake alters quazepam absorption. Therefore, the authors measured and compared pharmacokinetic parameters of quazepam taken in a fasted state and taken 30 minutes after consuming meals containing different amounts of dietary fat. A three-arm randomized crossover study was conducted. Nine healthy male volunteers took a single oral 20-mg dose of quazepam under the following conditions: (1) after fasting overnight for at least 12 hours, (2) 30 minutes after consuming a low-fat meal (two slices of bread and 200 ml of apple juice), or (3) 30 minutes after consuming high-fat meal (two slices of bread with 30 gm of butter and 200 ml of apple juice). Plasma concentrations of quazepam and its metabolite, 2-oxoquazepam, were monitored up to 48 hours after the dosing. In comparison with corresponding plasma values for quazepam taken in a fasting state, the peak concentrations (Cmax) of quazepam taken 30 minutes after consuming a low-fat meal and high-fat meal were 243% (90% confidence interval [CI] = 161%-325%) and 272% (90% CI = 190%-355%), respectively. Area under the plasma concentration-time curve from 0 to 8 hours (AUC(0-8)) and 0 to 48 hours (AUC(0-48)) of quazepam was increased with the low-fat meal by 2-fold (90% CI = 1.5- to 2.7-fold) and 1.4-fold (90% CI = 1.0- to 1.7-fold), respectively, and with the high-fat meal by 2.2-fold (90% CI = 1.3- to 3-fold) and 1.5-fold (90% CI = 0.7- to 2.4-fold), respectively. The pharmacokinetic change in 2-oxoquazepam to the parent compound was similar. Quazepam was well tolerated, with no significant difference in the Stanford Sleepiness Scale between fasted and fed conditions. These findings show that food intake has an evident effect on quazepam absorption, but further studies are needed to clarify a determinant factor of this alteration (2.5-fold for Cmax and 2.1-fold for AUC(0-8), on average). It might not be necessary to do dose adjustment with meal content because quazepam is well tolerated.
Norio Yasui-Furukori; Tsuyoshi Kondo; Takenori Takahata; Kazuo Mihara; Shingo Ono; Sunao Kaneko; Tomonori Tateishi
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  42     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-04     Completed Date:  2003-03-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1335-40     Citation Subset:  IM    
Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, Japan.
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MeSH Terms
Anti-Anxiety Agents / blood,  pharmacokinetics*
Area Under Curve
Cross-Over Studies
Dietary Fats / administration & dosage,  adverse effects*
Food-Drug Interactions*
Hypnotics and Sedatives / blood,  pharmacokinetics*
Postprandial Period
Time Factors
Reg. No./Substance:
0/Anti-Anxiety Agents; 0/Dietary Fats; 0/Hypnotics and Sedatives; 12794-10-4/Benzodiazepines; 36735-22-5/quazepam; 49606-44-2/2-oxoquazepam

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