title: Resolving the physiological conditions in bioavailability and bioequivalence studies: Comparison of fasted and fed state.
abstract: 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 5min 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 30mbar and 304mbar, whereas after fed state ingestion values of at least 240mbar 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.
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Schneider
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Koziolek
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Modeß
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Dokter
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Tarek
authors.initials: T
authors.lastname: Roustom
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Siegmund
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany. Electronic address: werner.weitschies@uni-greifswald.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Weitschies
mesh_terms: D000328:Adult; D001682:Biological Availability; D015992:Body Mass Index; D004063:Digestion; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005215:Fasting; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D005772:Gastrointestinal Transit / Q000502:physiology; D064368:Healthy Volunteers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D011312:Pressure; D012995:Solubility; D013270:Stomach / Q000187:drug effects; D013696:Temperature; D013810:Therapeutic Equivalency; D013997:Time Factors; D055815:Young Adult
chemical_list: D004337:Drug Carriers
keywords: Food effect; GI tract; Pressure; SmartPill; Temperature; Transit time; pH