Abstract：
:Increasing costs of research and development in the pharmaceutical industry has necessitated a growing interest in the early prediction of human pharmacokinetics of drug candidates. Of growing interest is the need to understand oral absorption, the most common route of small molecule drug administration. The fraction of dose absorbed (%Fa) is considered a critical yet challenging parameter to predict. A kinetic model has been developed and tested to provide an early prediction of the fraction dose absorbed in humans. Unlike the traditional plug-flow model, this model assumes first-order kinetics to estimate the amount of drug present in the stomach and small intestine as a function of time and calculates the amount of drug released and absorbed during the transit. Other variables can be included in calculation as a function of time to better mimic the physiological condition with this approach. Absorption efficiency is assigned along with %Fa to give a quantitative estimate of the limiting factor for oral absorption. The model was tested with literature and in-house compounds. It was found that this model gives a good prediction of human %Fa with a correction coefficient (R2) of 0.8 and greater between predicted and reported %Fa for all compounds.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Chiang PC,Liu J,Fan P,Wong Hdoi
10.1016/j.xphs.2018.03.015subject
Has Abstractpub_date
2018-07-01 00:00:00pages
1798-1805issue
7eissn
0022-3549issn
1520-6017pii
S0022-3549(18)30155-2journal_volume
107pub_type
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