In Vitro Studies are Sometimes Better than Conventional Human Pharmacokinetic In Vivo Studies in Assessing Bioequivalence of Immediate-Release Solid Oral Dosage Forms
Journal Title: The AAPS Journal - Year 2008, Vol 10, Issue 2
Abstract
Human pharmacokinetic in vivo studies are often presumed to serve as the “gold standard” to assess product bioequivalence (BE) of immediate-release (IR) solid oral dosage forms. However, when this general assumption is re-visited, it appears that in vitro studies are sometimes better than in vivo studies in assessing BE of IR solid oral dosage forms. Reasons for in vitro studies to sometimes serve as the better method are that in vitro studies: (a) reduce costs, (b) more directly assess product performance, and (c) offer benefits in terms of ethical considerations. Reduced costs are achieved through avoiding in vivo studies where BE is self-evident, where biopharmaceutic data anticipates BE, and where in vivo BE study type II error is high. In vitro studies more directly assess product performance than do conventional human pharmacokinetic BE studies, since in vitro studies focus on comparative drug absorption from the two products, while in vivo BE testing can suffer from complications due to its indirect approach. Regarding ethical considerations, in vitro studies better embrace the principle “No unnecessary human testing should be performed” and can result in faster development. Situations when in vitro test should be viewed as preferred include Class I drugs with rapid dissolution, Class III drugs with very rapid dissolution, and highly variable drugs with rapid dissolution and that are not bio(equivalence)problem drugs. Sponsors of potential in vivo human pharmacokinetic BE testing should be required to justify why in vitro data is insufficient, similar to proposed animal testing requires justification to not employ an in vitro approach.
Authors and Affiliations
James E. Polli
Keywords
Related Articles
- EP ID EP681557
- DOI 10.1208/s12248-008-9027-6
- Views 62
- Downloads 0
Simultaneous Analysis of Multiple Monoclonal Antibody Biotherapeutics by LC-MS/MS Method in Rat Plasma Following Cassette-Dosing
The online version of this article (doi:10.1208/s12248-012-9435-5) contains supplementary material, which is available to authorized users.
Targeted Delivery of Curcumin to Tumors via PEG-Derivatized FTS-Based Micellar System
The online version of this article (doi:10.1208/s12248-014-9595-6) contains supplementary material, which is available to authorized users.
Characterisation and Deposition Studies of Recrystallised Lactose from Binary Mixtures of Ethanol/Butanol for Improved Drug Delivery from Dry Powder Inhalers
The online version of this article (doi:10.1208/s12248-010-9241-x) contains supplementary material, which is available to authorized users.
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)
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 Admini...
Neuro-fuzzy Models as an IVIVR Tool and Their Applicability in Generic Drug Development
The online version of this article (doi:10.1208/s12248-014-9569-8) contains supplementary material, which is available to authorized users.