Resolving the physiological conditions in bioavailability and bioequivalence studies: Comparison of fasted and fed state

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• 作者：Felix Schneider^a ; Michael Grimm^a ; Mirko Koziolek^a ; Christiane Modeß ; ^b ; Anne Dokter^b ; Tarek Roustom^b ; Werner Siegmund^b ; Werner Weitschies^a ; ^{werner.weitschies@uni-greifswald.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：SmartPill ; Transit time ; Food effect ; GI tract ; Temperature ; Pressure ; pH
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：108
• 期：Complete
• 页码：214-219
• 全文大小：1602 K

文摘

In the present study temperature, pH and pressure profiles of nine healthy human volunteers were investigated after ingestion of the SmartPill® under conditions simulating the fasted state treatment in bioavailability and bioequivalence studies. In a previously published study the same subjects received the SmartPill® under fed conditions as recommended by the FDA. Since large non-digestible objects are mainly emptied during phase III of the interdigestive migrating motor complex, the gastric residence time of the SmartPill® was found to be clearly shorter under fasting conditions. Intragastric pH values during the initial 5 min were similar with an identical median value of pH 4.6. Interestingly, the median lowest observed intragastric pH value in fasted state was about one pH unit higher than that under fed conditions. Highest pressure activity was observed within the stomach, in relation to gastric emptying. In fasted state, pressure values upon gastric emptying varied strongly between 30 mbar and 304 mbar, whereas after fed state ingestion values of at least 240 mbar could always be observed. The data showed highly variable gastrointestinal parameters even under fasting conditions which must be considered when evaluating clinical studies and developing biorelevant in vitro test methods especially for large non-disintegrating dosage forms.