Current industrial practices of assessing permeability and P-glycoprotein interaction
Journal Title: The AAPS Journal - Year 2006, Vol 8, Issue 1
Abstract
Combination of the in vitro models that are high throughput but less predictive and the in vivo models that are low throughput but more predictive is used effectively to evaluate the intestinal permeability and transport characteristics of a large number of drug candidates during lead selection and lead optimization processes. Parallel artificial membrane permeability assay and Caco-2 cells are the most frequently used in vitro models to assess intestinal permeability. The popularity of these models stems from their potential for high throughput, cost effectiveness, and adequate predictability of absorption potential in humans. However, several caveats associated with these models (eg, poor predictability for transporter-mediated and paracellularly absorbed compounds, significant nonspecific binding to cells/devices leading to poor recovery, variability associated with experimental factors) need to be considered carefully to realize their full potential. P-glycoprotein, among other pharmaceutically relevant transporters, has been well demonstrated to be the major determinant of drug disposition. The review article presents an objective analysis of the permeability and transporter models currently being used in the pharmaceutical industry and could help guide the discovery scientists in implementing these models in an optimal fashion.
Authors and Affiliations
Praveen V. Balimane, Yong-Hae Han, Saeho Chong
Keywords
Related Articles
- EP ID EP681632
- DOI 10.1208/aapsj080101
- Views 91
- Downloads 0
A short-term (accelerated release) approach to evaluate peptide release from PLGA depot formulations
An accelerated method to evaluate peptide release from poly(dl-lactide-co-glycolide) (PLGA) depot formulations in short time is described. Peptide-loaded microspheres were made from hydrophilic 50∶50 PLGA by a di...
Survey of International Regulatory Bioequivalence Recommendations for Approval of Generic Topical Dermatological Drug Products
The objective of this article is to discuss the similarities and differences in accepted bioequivalence (BE) approaches for generic topical dermatological drug products between international regulatory authorities and or...
Appropriate calibration curve fitting in ligand binding assays
Calibration curves for ligand binding assays are generally characterized by a nonlinear relationship between the mean response and the analyte concentration. Typically, the response exhibits a sigmoidal relationship with...
Selected physical and chemical properties of commercial Hypericum perforatum extracts relevant for formulated product quality and performance
Objective. The complex composition-activity relationship of botanicals such as St John's Wort (SJW) presents a major challenge to product development, manufacture, and establishment of appropriate quality and performance...
Clinical Relevance of Dissolution Testing in Quality by Design
Quality by design (QbD) has recently been introduced in pharmaceutical product development in a regulatory context and the process of implementing such concepts in the drug approval process is presently on-going. This ha...