Population-Based Mechanistic Prediction of Oral Drug Absorption
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 2
Abstract
The bioavailability of drugs from oral formulations is influenced by many physiological factors including gastrointestinal fluid composition, pH and dynamics, transit and motility, and metabolism and transport, each of which may vary with age, gender, race, food, and disease. Therefore, oral bioavailability, particularly of poorly soluble and/or poorly permeable compounds and those that are extensively metabolized, often exhibits a high degree of inter- and intra-individual variability. While several models and algorithms have been developed to predict bioavailability in an average person, efforts to accommodate intrinsic variability in the component processes are less common. An approach that incorporates such variability for human populations within a mechanistic framework is described together with examples of its application to drug and formulation development.
Authors and Affiliations
Masoud Jamei, David Turner, Jiansong Yang, Sibylle Neuhoff, Sebastian Polak, Amin Rostami-Hodjegan, Geoffrey Tucker
Keywords
Related Articles
- EP ID EP681475
- DOI 10.1208/s12248-009-9099-y
- Views 104
- Downloads 0
The Population Pharmacokinetics of d -β-hydroxybutyrate Following Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate
The online version of this article (doi:10.1208/s12248-016-9879-0) contains supplementary material, which is available to authorized users.
Recent Advances in Application of Pharmacogenomics for Biotherapeutics
Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of their relatively high specificity, low off-target effec...
Specific Method Validation and Sample Analysis Approaches for Biocomparability Studies of Denosumab Addressing Method and Manufacture Site Changes
The online version of this article (doi:10.1208/s12248-012-9414-x) contains supplementary material, which is available to authorized users.
Current Industrial Practices in Assessing CYP450 Enzyme Induction: Preclinical and Clinical
Induction of drug metabolizing enzymes, such as the cytochromes P450 (CYP) is known to cause drug-drug interactions due to increased elimination of co-administered drugs. This increased elimination may lead to significan...
A novel in vitro release method for submicron-sized dispersed systems
Sink conditions are often violated when using conventional release methods for dispersed systems. A novel reverse dialysis bag method was designed to overcome this problem. Model drug transport rates from submicron emuls...