Inflammation induces changes in the functional expression of ABC
transporters: an overview of different models and consequences for drug
disposition
Abstract
The ATP-binding cassette (ABC) transporters play a key role in drug
pharmacokinetics. These membrane transporters are present in several
physiological barriers and they can be a source of pharmacokinetic
variability. Changes in ABC transporter expression and functionality may
consequently affect drug disposition resulting in different drug
exposure. Inflammation, present in several acute and chronic diseases,
has been identified as a source of modulation in drug transporter
expression leading to variability in drug response. Its regulation may
be particularly dangerous for drugs with a narrow therapeutic index. In
this context, numerous in vitro and in -vivo models have shown up- or
downregulation in the expression and functionality of ABC transporters
under inflammatory conditions. Nevertheless, the existence of nonagreed
data and the lack of standardization for the models used have led to a
more complex interpretation of these data. Thereby, the standardization
of study models is crucial to increase the relevance of data. In
addition, current data are not sufficient and further studies should be
performed to provide new evidence using additional techniques such as
mass spectrometry that will give more accurate quantitative information
about ABC transporter expression during inflammation.