Predicting the impact of physiological and biochemical processes on oral drug bioavailability

• Published in: Advanced drug delivery reviews Vol. 50; pp. S41 - S67
• Main Authors: Agoram, Balaji, Woltosz, Walter S., Bolger, Michael B.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier B.V 01.10.2001; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Biological Availability; Carrier-mediated transport and efflux; Computer Simulation; Drug absorption; General pharmacology; Humans; In silico simulation; Intestinal Absorption; Medical sciences; Models, Biological; Pharmaceutical Preparations - metabolism; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Saturable P450 metabolism; In silico simulation; Carrier-mediated transport and efflux; Saturable P450 metabolism; Drug absorption; Digoxin; Liver; Biological transport; Review; Modeling; Conveyor; Saquinavir; Absorption; First pass effect; Benzodiazepine derivatives; Glycoside; Mathematical model; Propranolol; Digitalis drug; Human; Digestive system; Gut; Prediction; Oral administration; Metabolism; In vitro; In vivo; Animal; Midazolam; Pharmacokinetics
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/S0169-409X(01)00179-X

Recent advances in computational methods applied to the fields of drug delivery and biopharmaceutics will be reviewed with a focus on prediction of the impact of physiological and biochemical factors on simulation of gastrointestinal absorption and bioavailability. Our application of a gastrointestinal simulation for the prediction of oral drug absorption and bioavailability will be described. First, we collected literature data or we estimated biopharmaceutical properties by application of statistical methods to a set of 2D and 3D molecular descriptors. Second, we integrated the differential equations for an advanced compartmental absorption and transit (ACAT) model in order to determine the rate, extent, and approximate gastrointestinal location of drug liberation (for controlled release), dissolution, passive and carrier-mediated absorption, and saturable metabolism and efflux. We predict fraction absorbed, bioavailability, and C p vs. time profiles for common drugs and compare those estimates to literature data. We illustrate the simulated impact of physiological and biochemical processes on oral drug bioavailability.