Intestinal flow rates, absorption of felodipine from the small intestine and attributes of chyme collected at midgut from Labradors

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Show simple item record Diebold, Steffen M. 2023-11-09T11:40:14Z 2023-11-09T11:40:14Z 2023
dc.identifier.uri de_DE
dc.description.abstract The objectives of the present study were (1) to investigate gastrointestinal hydrodynamics of Labradors as a model for human midgut (2) to examine various attributes of intestinal fluids in vivo and (3) to study the influence of hydrodynamics on the dissolution and absorption of a poorly soluble drug from various suspensions. Gastrointestinal flow rates were determined volumetrically using an aspiration method. Isotonic saline and 20 % glucose solutions were used to alter gastrointestinal hydrodynamics. Felodipine, a BCS class II substance, was suspended in these fluids. Osmolality, pH, bile acid concentration and drug solubility in various chyme samples were determined. Blood plasma levels of felodipine were recorded while gastrointestinal dissolution was ongoing. Fluid recovery at midgut fistula was significantly higher (>100 %) for glucose 20 % than for isotonic saline solutions (70 %). After administration of 200 ml glucose 20 % the (overall) grand median of differential gastrointestinal flow rates (DFR) was 8.3 ml/min.. Individual spike flow ranged from 20 up to 60 ml/min. Corresponding flow rates after administration of 200 ml isotonic saline were 35.0 ml/min. for the grand median including individual spike flows beyond 100 ml/min.. Within and between-dog variability in flow rate data was similar. In general, glucose solutions released more evenly. Following oral administration of glucose solution 20 % osmolality of intestinal fluids decreased within 40 min. from about 1000 mOsm. towards more physiological values of about 350 mOsm.. Saturation solubility of felodipine (Cs) in jejunal chyme after administration of either solution (saline or glucose) was determined to be about 10 (µg/ml) on average (median), exposing high variability with time! The intestinal solubility varied greatly within the course of an experiment. However, a strong correlation was observed between the aspirated fluid volume and the dissolved amount of felodipine confirming the well known relationship of Noyes, Whitney, Nernst and Brunner in-vivo. Grand median of pH in jejunal chyme of labradors was determined to be 6.68. Median values range from 4.38-7.62. The pharmacokinetic data showed a slight trend to differences based on particle size and on fluid administered. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.ddc 590 de_DE
dc.subject.ddc 610 de_DE
dc.subject.ddc 630 de_DE
dc.subject.other in vivo hydrodynamics en
dc.subject.other in vivo dissolution en
dc.subject.other osmolality en
dc.subject.other pH en
dc.subject.other chyme en
dc.subject.other gastric emptying en
dc.subject.other intestinal transit en
dc.subject.other particle size en
dc.subject.other human midgut en
dc.subject.other small intestine en
dc.subject.other glucose en
dc.subject.other saline en
dc.subject.other felodipine en
dc.subject.other dog model en
dc.subject.other poorly soluble drug en
dc.subject.other flow rate en
dc.subject.other transit rate en
dc.subject.other bile acid en
dc.subject.other fistula en
dc.subject.other aspiration method en
dc.title Intestinal flow rates, absorption of felodipine from the small intestine and attributes of chyme collected at midgut from Labradors en
dc.type Article de_DE
utue.publikation.fachbereich Pharmazie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE
utue.publikation.noppn yes de_DE


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