2023, Diebold, Steffen M.

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.

2017, Schmale, Julia, Henning, Silvia, Henzing, Bas, Keskinen, Helmi, Sellegri, Karine, Ovadnevaite, Jurgita, Bougiatioti, Aikaterini, Kalivitis, Nikos, Stavroulas, Iasonas, Jefferson, Anne, Park, Minsu, Schlag, Patrick, Kristensson, Adam, Iwamoto, Yoko, Pringle, Kirsty, Reddington, Carly, Aalto, Pasi, Äijälä, Mikko, Baltensperger, Urs, Bialek, Jakub, Birmili, Wolfram, Bukowiecki, Nicolas, Ehn, Mikael, Fjæraa, Ann Mari, Fiebig, Markus, Frank, Göran, Fröhlich, Roman, Frumau, Arnoud, Furuya, Masaki, Hammer, Emanuel, Heikkinen, Liine, Herrmann, Erik, Holzinger, Rupert, Hyono, Hiroyuki, Kanakidou, Maria, Kiendler-Scharr, Astrid, Kinouchi, Kento, Kos, Gerard, Kulmala, Markku, Mihalopoulos, Nikolaos, Motos, Ghislain, Nenes, Athanasios, O’Dowd, Colin, Paramonov, Mikhail, Petäjä, Tuukka, Picard, David, Poulain, Laurent, Prévôt, André Stephan Henry, Slowik, Jay, Sonntag, Andre, Swietlicki, Erik, Svenningsson, Birgitta, Tsurumaru, Hiroshi, Wiedensohler, Alfred, Wittbom, Cerina, Ogren, John A., Matsuki, Atsushi, Yum, Seong Soo, Myhre, Cathrine Lund, Carslaw, Ken, Stratmann, Frank, Gysel, Martin

Cloud condensation nuclei (CCN) number concentrations alongside with submicrometer particle number size distributions and particle chemical composition have been measured at atmospheric observatories of the Aerosols, Clouds, and Trace gases Research InfraStructure (ACTRIS) as well as other international sites over multiple years. Here, harmonized data records from 11 observatories are summarized, spanning 98,677 instrument hours for CCN data, 157,880 for particle number size distributions, and 70,817 for chemical composition data. The observatories represent nine different environments, e.g., Arctic, Atlantic, Pacific and Mediterranean maritime, boreal forest, or high alpine atmospheric conditions. This is a unique collection of aerosol particle properties most relevant for studying aerosol-cloud interactions which constitute the largest uncertainty in anthropogenic radiative forcing of the climate. The dataset is appropriate for comprehensive aerosol characterization (e.g., closure studies of CCN), model-measurement intercomparison and satellite retrieval method evaluation, among others. Data have been acquired and processed following international recommendations for quality assurance and have undergone multiple stages of quality assessment.