PURPOSE: The development and validation of a physiology-based absorption model for orally administered drugs in monkeys is described. MATERIALS AND METHODS: Physiological parameters affecting intestinal transit and absorption of an orally administered drug in monkeys have been collected from the literature and implemented in a physiological model for passive absorption previously developed for rats and humans. Predicted fractions of dose absorbed have been compared to experimentally observed values for a set of N = 37 chemically diverse drugs. A sensitivity analysis was performed to assess the influence of various physiological model parameters on the predicted fraction dose absorbed. RESULTS: A Pearson's correlation coefficient of 0.94 (95% confidence interval: [0.88, 0.97]; p < 0.0001) between the predicted and observed fraction dose absorbed in monkeys was obtained for compounds undergoing non-solubility limited passive absorption (N = 29). The sensitivity analysis revealed that the predictions of fractions dose absorbed in monkeys are very sensitive with respect to inter-individual variations of the small intestinal transit time. CONCLUSIONS: The model is well suited to predict the fraction dose absorbed of passively absorbed compounds after oral administration and to assess the influence of inter-individual physiological variability on oral absorption in monkeys.
PURPOSE: The development and validation of a physiology-based absorption model for orally administered drugs in monkeys is described. MATERIALS AND METHODS: Physiological parameters affecting intestinal transit and absorption of an orally administered drug in monkeys have been collected from the literature and implemented in a physiological model for passive absorption previously developed for rats and humans. Predicted fractions of dose absorbed have been compared to experimentally observed values for a set of N = 37 chemically diverse drugs. A sensitivity analysis was performed to assess the influence of various physiological model parameters on the predicted fraction dose absorbed. RESULTS: A Pearson's correlation coefficient of 0.94 (95% confidence interval: [0.88, 0.97]; p < 0.0001) between the predicted and observed fraction dose absorbed in monkeys was obtained for compounds undergoing non-solubility limited passive absorption (N = 29). The sensitivity analysis revealed that the predictions of fractions dose absorbed in monkeys are very sensitive with respect to inter-individual variations of the small intestinal transit time. CONCLUSIONS: The model is well suited to predict the fraction dose absorbed of passively absorbed compounds after oral administration and to assess the influence of inter-individual physiological variability on oral absorption in monkeys.
Authors: David S Wishart; Craig Knox; An Chi Guo; Savita Shrivastava; Murtaza Hassanali; Paul Stothard; Zhan Chang; Jennifer Woolsey Journal: Nucleic Acids Res Date: 2006-01-01 Impact factor: 16.971
Authors: Mahmoud E Soliman; Adeniyi T Adewumi; Oluwole B Akawa; Temitayo I Subair; Felix O Okunlola; Oluwayimika E Akinsuku; Shahzeb Khan Journal: AAPS PharmSciTech Date: 2022-03-15 Impact factor: 3.246
Authors: Thomas Eissing; Lars Kuepfer; Corina Becker; Michael Block; Katrin Coboeken; Thomas Gaub; Linus Goerlitz; Juergen Jaeger; Roland Loosen; Bernd Ludewig; Michaela Meyer; Christoph Niederalt; Michael Sevestre; Hans-Ulrich Siegmund; Juri Solodenko; Kirstin Thelen; Ulrich Telle; Wolfgang Weiss; Thomas Wendl; Stefan Willmann; Joerg Lippert Journal: Front Physiol Date: 2011-02-24 Impact factor: 4.566