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The following message was posted to: PharmPK
Would anyone care to comment on the utility of MDCK vs. Caco-2
permeability assays? ...the pros and cons of each and what information
one can extrapolate, pitfalls etc.
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The most obvious difference is the origin of these cell lines. MDCK
cells are a canine kidney cell line whereas Caco-2 cells are colon
derived, from a human carcinoma. Thus, species differences are present,
and these will inherently affect substrate specificities, and drug
concentrations. Furthermore, if you are using them as a permeability
model, there are vast differences in transporter levels (such PGP,
MRPs), and even Cytochrome P450 levels are different. These
differences, and others (Isc) can greatly affect pharmacokinetic
parameters measured, and drug permeability. Although you did not
mention for what purpose these two cell lines are considered, they must
be considered in the context that they are intended to be used.
[Second message - db]
You also asked about the pros and cons of each. Although I am not as
familiar with MDCK cells, I will comment briefly on Caco-2.
- Human derived, therefore able to extrapolate data to some extent to
- Very commonly used, a well accepted model of drug permeability
- High throughput is easily possible
- Levels of Cytochrome P450 (specifically CYP3A4, the CYP responsible
for the metabolism of approx. 50% of current therapeutic agents) is not
consistent with humans, in that they are expressed at extremely low
levels. Induction of CYP3A4is possible, using Vitamin D
pre-treatment. However, it is not known to what level these are
induced, and whether these levels are normal.
- P-glycoprotein levels are high
- The tight junctions are "very tight" such that drug permeability
profiles are reduced in magnitude as compared to human intestinal
Many papers and books have been written on both the utility of Caco-2
cells, as well as MDCK cells by RT Borchardt.
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