title: Gastrointestinal Motility Variation and Implications for Plasma Level Variation: Oral Drug Products.
abstract: The oral route of administration is still by far the most ubiquitous method of drug delivery. Development in this area still faces many challenges due to the complexity and inhomogeneity of the gastrointestinal environment. In particular, dosing unpredictably relative to motility phase means the gastrointestinal environment is a random variable within a defined range. Here, we present a mass balance analysis that captures this variation and highlights the effects of gastrointestinal motility, exploring what impacts it ultimately has on plasma levels and the relationship to bioequivalence for high solubility products with both high and low permeability (BCS I and III). Motility-dependent compartmental absorption and transit (MDCAT) mechanistic analysis is developed to describe the underlying fasted state cyclical motility and how the contents of the gastrointestinal tract are propelled.
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Arjang
authors.initials: A
authors.lastname: Talattof
authors.affiliation: Tulsa, Oklahoma 74136, United States.
authors.forename: Judy C
authors.initials: JC
authors.lastname: Price
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
mesh_terms: D000284:Administration, Oral; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003198:Computer Simulation; D004049:Diethylcarbamazine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000077340:Fluvastatin; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007211:Indoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008954:Models, Biological; D014018:Tissue Distribution
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007166:Immunosuppressive Agents; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D000077340:Fluvastatin; D005472:Fluorouracil; D004049:Diethylcarbamazine
keywords: bioequivalence; clinical trial simulation; gastric emptying; mechanistic physiological model; migrating motor complex; motility; oral dosage