Scientific Perspectives on Extending the Provision for Waivers of In vivo Bioavailability and Bioequivalence Studies for Drug Products Containing High Solubility-Low Permeability Drugs (BCS-Class 3)
Journal Title: The AAPS Journal - Year 2008, Vol 10, Issue 2
Abstract
Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA–BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility–Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.
Authors and Affiliations
Salomon Stavchansky
Keywords
Related Articles
- EP ID EP681559
- DOI 10.1208/s12248-008-9030-y
- Views 84
- Downloads 0
Organic Cation Transporter OCTs (SLC22) and MATEs (SLC47) in the Human Kidney
In the kidney, human organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are the major transporters for the secretion of cationic drugs into the urine. In the human kidney, OCT2 mediates...
Assuring quality and performance of sustained and controlled release parenterals: Workshop report
This is a summary report of the American Association of Pharmaceutical Scientists, the Food and Drug Administration and the United States Pharmacopoeia cosponsored workshop on “Assuring Quality and Performance of...
PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression
Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity and unsatisfied in vivo efficacy limit...
A Priori Identifiability of Target-Mediated Drug Disposition Models and Approximations
The online version of this article (doi:10.1208/s12248-015-9795-8) contains supplementary material, which is available to authorized users.
Cannabinoid receptors and endocannabinoids: Evidence for new players
It is now well established that the psychoactive effects ofCannabis sativa are primarily mediated through neuronal CB1 receptors, while its therapeutic immune properties are primarily mediated through CB2 receptors. Two...