title: Impact of Luminal Fluid Volume on the Drug Absorption After Oral Administration: Analysis Based on In Vivo Drug Concentration-Time Profile in the Gastrointestinal Tract.
abstract: The objective of this study is to clarify the influence of fluid volume in the gastrointestinal (GI) tract on the oral drug absorption. In vivo rat luminal concentrations of FITC-dextran (FD-4), a nonabsorbable marker, and drugs (metoprolol and atenolol) after oral coadministration as solutions with different osmolarity were determined by direct sampling of residual water in each segment of the GI tract. The luminal FD-4 concentration after oral administration as hyposmotic solution was significantly higher than that after administration as isosmotic or hyperosmotic solution. As the change in FD-4 concentration reflects the change in the volume of luminal fluid, it indicated that the luminal volume was greatly influenced by osmolality of solution ingested orally. Then, fraction of drug absorbed (Fa) in these segments was calculated by comparing the area under the luminal concentration-time curve of FD-4 with those of drugs. Fa values of two model drugs in each GI segment decreased with increase in luminal fluid volume, and the impact of the fluid volume was marked for Fa of atenolol (a low permeable drug) than for that of metoprolol (a high permeable drug). These findings should be beneficial to assure the effectiveness and safety of oral drug therapy.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima, 737-0112, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Depertment of Corporate Quality Assurance, Kyowa Pharmaceutical Industry Company, Ltd., Yodogawa-ku, Osaka, 532-0011, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Goto
authors.affiliation: Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kataoka
authors.affiliation: Laboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
authors.affiliation: Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001262:Atenolol / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism*; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D008790:Metoprolol / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D001262:Atenolol; D008790:Metoprolol; D016650:Fluorescein-5-isothiocyanate
keywords: biopharmaceutics classification system; gastrointestinal; luminal volume; oral absorption; osmolality; passive diffusion; permeability