Clarysse S, Tack J, Lammert F, Duchateau G, Reppas C, Augustijns P
Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Campus Gasthuisberg O&N 2 (Box 921), Herestraat 49, 3000 Leuven, Belgium.
J Pharm Sci. 2009 Mar;98(3):1177-92. doi: 10.1002/jps.21502.
The purpose of this study was to assess the changes in duodenal composition in three nutritional states: fasted, fed, and fat-enriched fed state. Two isocaloric meals were administered to healthy subjects on nonconsecutive days. Subsequently, duodenal samples were collected every 30 min after which they were characterized with respect to pH, lipolytic products, bile salts, phospholipids, osmolality, and surface tension. The resulting time profiles displayed fluctuating patterns, which reflect high inter- and intrasubject variability. Duodenal composition was not altered by the higher fat percentage of the fat-enriched liquid meal. Monoglycerides, amounting from 5% to 88% of total lipids, were the dominant lipolytic species, followed by free fatty acids. Within 30 min after meal administration, individual intraduodenal concentrations of lipid products were 0.0-5.5, 1.0-14.9, and 3.1-22.4 mg/mL in fasted, fed, and fat-enriched fed state, respectively. The corresponding values for bile salts were 2.0-9.0, 6.9-9.3, and 4.4-30.3 mM and for phospholipids 0.06-2.4, 2.6-5.7, and 1.4-9.3 mM, respectively. Specific trends though, were not detected. This study illustrates the variable intraluminal conditions that can result after food intake. As intraduodenal events (e.g., intraduodenal dissolution) affect absorption of poorly water soluble and/or highly lipophilic drugs, this variability may possibly contribute to the highly variable drug plasma-time profiles often observed.
禁食、进食和高脂进食状态。在非连续的日子里给健康受试者提供两份等热量的餐食。随后，每隔30分钟采集十二指肠样本，然后对其pH值、脂解产物、胆汁盐、磷脂、渗透压和表面张力进行表征。所得的时间曲线呈现出波动模式，这反映了受试者之间和受试者内部的高度变异性。高脂液体餐中较高的脂肪百分比并未改变十二指肠成分。甘油单酯占总脂质的5%至88%，是主要的脂解产物，其次是游离脂肪酸。在进食后30分钟内，禁食、进食和高脂进食状态下十二指肠内脂质产物的个体浓度分别为0.0 - 5.5、1.0 - 14.9和3.1 - 22.4 mg/mL。胆汁盐的相应值分别为2.0 - 9.0、6.9 - 9.3和4.4 - 30.3 mM，磷脂的相应值分别为0.06 - 2.4、2.6 - 5.7和1.4 - 9.3 mM。不过，未检测到特定趋势。本研究说明了进食后可能导致的管腔内条件的变化。由于十二指肠内事件（如十二指肠内溶解）会影响水溶性差和/或高度亲脂性药物的吸收，这种变异性可能会导致经常观察到的药物血浆时间曲线高度可变。
