title: Prediction of drug intestinal absorption in human using the Ussing chamber system: A comparison of intestinal tissues from animals and humans.
abstract: An adequate evaluation system for drug intestinal absorption is essential in the pharmaceutical industry. Previously, we established a novel prediction system of drug intestinal absorption in humans, using the mini-Ussing chamber equipped with human intestinal tissues. In this system, the TI value was defined as the sum of drug amounts transported to the basal-side component (Xcorr) and drug amounts accumulated in the tissue (Tcorr), which are normalized by AUC of a drug in the apical compartment, as an index for drug absorption. In order to apply this system to the screening assay, it is important to understand the differences between animal and human tissues in the intestinal absorption of drugs. In this study, the transport index (TI) values of three drugs, with different levels of membrane permeability, were determined to evaluate the rank order of drug absorbability in intestinal tissues from rats, dogs, and monkeys. The TI values in small intestinal tissues in rats and dogs showed a good correlation with those in humans. On the other hand, the correlation of TI values in monkeys was lower compared to rats and dogs. The rank order of the correlation coefficient between human and investigated animal tissues was as follows: dog (r2=0.978), rat (r2=0.955), and monkey (r2=0.620). TI values in large intestinal tissues from rats (r2=0.929) and dogs (r2=0.808) also showed a good correlation. The obtained TI values in small intestinal tissues in rats and dogs were well correlated with the fraction of drug absorbed (Fa) in humans. From these results, the mini-Ussing chamber, equipped with intestinal tissues in rats and dogs, would be useful as a screening tool in the drug discovery stage. In addition, the obtained TI values can be used for the prediction of the Fain humans.
authors.affiliation: Bioavailability Research Project, Formulation Research Institute, Otsuka Pharmaceutical Co. Ltd., 224-18 Ebisuno Hiraishi Kawauchi-cho, Tokushima 771-0182, Japan. Electronic address: Miyake.Masateru@otsuka.jp.
authors.forename: Masateru
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd., 460-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Koga
authors.affiliation: Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd., 460-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd., 460-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yoda
authors.affiliation: Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd., 460-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan; Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC6018, Cincinnati, OH 45229-3039, USA.
authors.forename: Chie
authors.initials: C
authors.lastname: Emoto
authors.affiliation: Bioavailability Research Project, Formulation Research Institute, Otsuka Pharmaceutical Co. Ltd., 224-18 Ebisuno Hiraishi Kawauchi-cho, Tokushima 771-0182, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mukai
authors.affiliation: Bioavailability Research Project, Formulation Research Institute, Otsuka Pharmaceutical Co. Ltd., 224-18 Ebisuno Hiraishi Kawauchi-cho, Tokushima 771-0182, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Toguchi
mesh_terms: D000818:Animals; D001262:Atenolol / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015194:Diffusion Chambers, Culture; D004285:Dogs; D005544:Forecasting; D000882:Haplorhini; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008790:Metoprolol / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D001262:Atenolol; D008790:Metoprolol
keywords: Intestinal absorption; animal tissues; mini-Ussing chamber; prediction; transport index (TI)