Application of Method Suitability for Drug Permeability Classification
Journal Title: The AAPS Journal - Year 2010, Vol 12, Issue 4
Abstract
Experimental models of permeability in animals, excised tissues, cell monolayers, and artificial membranes are important during drug discovery and development as permeability is one of several factors affecting the intestinal absorption of oral drug products. The utility of these models is demonstrated by their ability to predict a drug’s in vivo intestinal absorption. Within the various permeability models, there are differences in the performance of the assays, along with variability in animal species, tissue sources, and cell types, resulting in a variety of experimental permeability values for the same drug among laboratories. This has led to a need for assay standardization within laboratories to ensure applicability in the drug development process. Method suitability provides a generalized approach to standardize and validate a permeability model within a laboratory. First, assay methodology is optimized and validated for its various experimental parameters along with acceptance criteria for the assay. Second, the suitability of the model is demonstrated by a rank order relationship between experimental permeability values and human extent of absorption of known model compounds. Lastly, standard compounds are employed to classify a test drug’s intestinal permeability and ensure assay reproducibility and quality. This review will provide examples of the different aspects method suitability for in situ (intestinal perfusions), ex vivo (everted intestinal sacs, diffusion chambers), and in vitro (cell monolayers, artificial membranes) experimental permeability models. Through assay standardization, reference standards, and acceptance criteria, method suitability assures the dependability of experimental data to predict a drug’s intestinal permeability during discovery, development, and regulatory application.
Authors and Affiliations
Donna A. Volpe
Keywords
Related Articles
- EP ID EP681411
- DOI 10.1208/s12248-010-9227-8
- Views 72
- Downloads 0
Comparative Pharmacology and Toxicology of Pharmaceuticals in the Environment: Diphenhydramine Protection of Diazinon Toxicity in Danio rerio but Not Daphnia magna
Pharmaceuticals and other contaminants of emerging concern present unique challenges to environmental risk assessment and management. Fortunately, mammalian pharmacology and toxicology safety data are more readily availa...
Commentary: Current Perspectives on the Aggregation of Protein Drugs
Erratum to: Autoradiography, MALDI-MS, and SIMS-MS Imaging in Pharmaceutical Discovery and Development
This article was published with incorrect reference citations in the permission notes in the legends for Figures  8 and 9. The permission note for Figure 8 should read: (Adapted with permission from Ref....
Regioselective Glucuronidation of Andrographolide and Its Major Derivatives: Metabolite Identification, Isozyme Contribution, and Species Differences
The online version of this article (doi:10.1208/s12248-014-9658-8) contains supplementary material, which is available to authorized users.
Pharmacodynamic Model of Sodium–Glucose Transporter 2 (SGLT2) Inhibition: Implications for Quantitative Translational Pharmacology
Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through incre...