caa a22 4500 477126642 CHVBK 20180405111651.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012148300807 doi (NATIONALLICENCE)springer-10.1023/A:1012148300807 Improved Prediction of In Vivo Peroral Absorption from In Vitro Intestinal Permeability Using an Internal Standard to Control for Intra- and Inter-Rat Variability [Elektronische Daten] [Martin Dowty, Charles Dietsch] Purpose. To evaluate the use of an in vitrointestinal permeability model to predict rat and human absorption as well as to evaluate the use of an internal standard to control for intra- and inter-rat variability. Methods. In vivoperoral absorption and in vitro steady-state intestinal permeability coefficients were determined in the rat for a variety of structurally different compounds with different physicochemical properties including: progesterone, hydrocortisone, salicylic acid, caffeine, clonidine, p-aminoclonidine, UK-14304, oxymetazoline, mannitol, PEG 900, PEG 4000, and a number of novel hydrophilic chemical entities. Results. The intestinal permeability coefficients determined in vitro could be used to predict the peroral absorption of a compound in both the rat and human. Normalizing the permeability of a test compound to an internal standard, e.g. mannitol, greatly improved the prediction of peroral absorption. Conclusions. The use of an internal standard can aid in the prediction of the peroral absorption of a test compound, in particular, for one that has moderate absorption in the range of 20−80%. Moreover, these methods would appear to be a useful means to improve the prediction of other absorption models as well, such as the Caco-2 cell systems and in-situ perfusion methods. Plenum Publishing Corporation, 1997 peroral absorption nationallicence in vitro/in vivo correlation nationallicence in vitro intestinal permeability nationallicence in vivo mass-balance nationallicence Ussing chamber nationallicence rat nationallicence Dowty Martin Health Care Research Center, Procter and Gamble Pharmaceuticals, 45040, Mason, Ohio aut Dietsch Charles Health Care Research Center, Procter and Gamble Pharmaceuticals, 45040, Mason, Ohio aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1792-1797 0724-8741 14:12<1792 1997 14 11095 https://doi.org/10.1023/A:1012148300807 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012148300807 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dowty Martin Health Care Research Center, Procter and Gamble Pharmaceuticals, 45040, Mason, Ohio aut NATIONALLICENCE 700 1- Dietsch Charles Health Care Research Center, Procter and Gamble Pharmaceuticals, 45040, Mason, Ohio aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1792-1797 0724-8741 14:12<1792 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer