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Clarysse, S.; Tack, J.; Lammert, F.; Duchateau, G.; Reppas, C.; Augustijns, P.
Journal of pharmaceutical sciences, March 2009, Letnik: 98, Številka: 3Journal Article
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 30min 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 30min after meal administration, individual intraduodenal concentrations of lipid products were 0.0–5.5, 1.0–14.9, and 3.1–22.4mg/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 4.4–30.3mM and for phospholipids 0.06–2.4, 2.6–5.7, and 1.4–9.3mM, 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.
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