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Effect of Dietary Fat Content in Meals on Pharmacokinetics of Quazepam
Author(s) -
YasuiFurukori Norio,
Kondo Tsuyoshi,
Takahata Takenori,
Mihara Kazuo,
Ono Shingo,
Kaneko Sunao,
Tateishi Tomonori
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270002042012004
Subject(s) - meal , pharmacokinetics , crossover study , metabolite , cmax , hypnotic , medicine , chemistry , food science , pharmacology , endocrinology , placebo , alternative medicine , pathology
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 (C max ) 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 toclarifya determinant factor of this alternation (2.5‐ fold for C max 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.