Emilie Hénin1,2, Martin Bergstrand3, Werner Weitschies4, Mats O Karlsson3. 1. Pharmacometrics Group, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden. emilie.henin@gmail.com. 2. Université Claude Bernard, EMR 3738 Ciblage Thérapeutique en Oncologie - Faculté de Médecine Lyon Sud, BP12, 69921, Oullins Cedex, France. emilie.henin@gmail.com. 3. Pharmacometrics Group, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden. 4. Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Greifswald, D-17487, Germany.
Abstract
PURPOSE: To develop a model predicting movement of non-disintegrating single unit dosage forms (or "tablet") through the gastrointestinal tract and characterizing the effect of food intake, based on Magnetic Marker Monitoring data, allowing real-time location of a magnetically labeled formulation. METHODS: Five studies including 30 individuals in 94 occasions under 3 food status were considered. The mean residence time (MRT) of the tablet and the effect of food intake in proximal (PS) and distal stomach (DS), small intestine (SI), ascending (AC), transverse (TC) and descending colon (DC) were estimated using a Markov model for probabilities of movement. RESULTS: Under fasting conditions, tablet MRTs were 9.4 min in PS, 10.4 in DS, 246 in SI, 545 in AC, 135 in TC, and 286 in DC. A meal taken simultaneous to tablet intake prolonged tablet MRT to 99 min in PS and to 232 in DS; probability of gastric emptying increased of 89% each hour from 2.25 h after meal. The effect of a gastroileac reflex, caused by a secondary meal, accelerated the transit from terminal SI to AC. CONCLUSION: This model-based knowledge can be used as a part of mechanism-based models for drug absorption, applied for bottom-up predictions and/or top-down estimation.
PURPOSE: To develop a model predicting movement of non-disintegrating single unit dosage forms (or "tablet") through the gastrointestinal tract and characterizing the effect of food intake, based on Magnetic Marker Monitoring data, allowing real-time location of a magnetically labeled formulation. METHODS: Five studies including 30 individuals in 94 occasions under 3 food status were considered. The mean residence time (MRT) of the tablet and the effect of food intake in proximal (PS) and distal stomach (DS), small intestine (SI), ascending (AC), transverse (TC) and descending colon (DC) were estimated using a Markov model for probabilities of movement. RESULTS: Under fasting conditions, tablet MRTs were 9.4 min in PS, 10.4 in DS, 246 in SI, 545 in AC, 135 in TC, and 286 in DC. A meal taken simultaneous to tablet intake prolonged tablet MRT to 99 min in PS and to 232 in DS; probability of gastric emptying increased of 89% each hour from 2.25 h after meal. The effect of a gastroileac reflex, caused by a secondary meal, accelerated the transit from terminal SI to AC. CONCLUSION: This model-based knowledge can be used as a part of mechanism-based models for drug absorption, applied for bottom-up predictions and/or top-down estimation.
Entities:
Keywords:
Food effect; GI transit; Markov model; Tablet movement
Authors: W Weitschies; C Friedrich; R S Wedemeyer; M Schmidtmann; O Kosch; M Kinzig; L Trahms; F Sörgel; W Siegmund; S Horkovics-Kovats; F Schwarz; J Raneburger; H Mönnikes Journal: Eur J Pharm Biopharm Date: 2008-06-05 Impact factor: 5.571
Authors: Benjamin Guiastrennec; Erik Söderlind; Sara Richardson; Alexandra Peric; Martin Bergstrand Journal: Pharm Res Date: 2017-02-02 Impact factor: 4.200