caa a22 4500 477127711 CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970801xx s 000 0 eng 10.1023/A:1012101311826 doi (NATIONALLICENCE)springer-10.1023/A:1012101311826 Mechanisms of Food Effects of Structurally Related Antiarrhythmic Drugs, Disopyramide and Bidisomide in the Rat [Elektronische Daten] [Kyu-Hyun Lee, Guang-Xin Xu, Grant Schoenhard, Chyung Cook] Purpose. To determine whether the rat is a good animal model for the food effects observed with bidisomide but not with the structurally similar antiarrhythmic drug, disopyramide in man and to explore a reason for the differences in the food effects of these compounds. Methods. The following effects on the absorption of bidisomide and/ or disopyramide were examined in the rat: Food effects, gastrointestinal transit time under fasting and nonfasting conditions, pH effects, hypertonic solution effect of NaCl and glucose, bile effects, permeability, inhibitory effects by Gly, Gly-Gly, Gly-Pro, glucose and mannitol and drug binding to food. Results. Remarkable food effects were observed with bidisomide but not with disopyramide. There was no difference in the GI transit time with and without food. The pH effect with and without food was similar. Effect of salt concentrations on bidisomide and disopyramide was similar. There was no bile effect on absorption of both compounds. Binding of bidisomide and disopyramide to food was similarly low. The apparent permeability of bidisomide was much lower than disopyramide especially in the ileum and its absorption was more inhibited by Gly, Gly-Gly and Gly-Pro. Conclusions. In the rat, as previously seen in humans, the food effect was observed with bidisomide but not with disopyramide. This difference was in part due to both lower intestinal permeability of bidisomide compared to disopyramide and greater inhibition of absorption by the amino acid, Gly and the dipeptides, Gly-Gly and Gly-Pro. Plenum Publishing Corporation, 1997 food effect nationallicence disopyramide nationallicence bidisomide nationallicence rat nationallicence Lee Kyu-Hyun Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut Xu Guang-Xin Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut Schoenhard Grant Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut Cook Chyung Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/8(1997-08-01), 1030-1038 0724-8741 14:8<1030 1997 14 11095 https://doi.org/10.1023/A:1012101311826 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012101311826 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lee Kyu-Hyun Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut NATIONALLICENCE 700 1- Xu Guang-Xin Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut NATIONALLICENCE 700 1- Schoenhard Grant Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut NATIONALLICENCE 700 1- Cook Chyung Pharmacokinetics, Bioanalytical and Radiochemistry, G. D. Searle & Co., 4901 Searle Parkway, 60077, Skokie, Illinois aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/8(1997-08-01), 1030-1038 0724-8741 14:8<1030 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer