alexa Evaluation of an accelerated Caco-2 cell permeability model.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Liang E, Chessic K, Yazdanian M

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Abstract An accelerated 3-7-day Caco-2 cell permeability model was examined and compared to the traditional 21-25-day model. Caco-2 cell permeability coefficients (P(Caco-2)) of 33 structurally diverse small molecular weight compounds from apical to basolateral (AP-->BL) direction in the accelerated model were approximately twice those in the traditional model. As observed with microscopy and transepithelial electrical resistance measurements, this difference was attributed to less confluent and differentiated Caco-2 cell monolayers in the accelerated model. However, there were no significant differences in rank ordering of the compounds. The expression of P-glycoprotein in the accelerated model was shown to be significantly less than that in the traditional model. This resulted in lower permeability directional ratios defined as the ratio between permeability coefficients from BL-->AP and from AP-->BL for compounds that were cellular efflux pump substrates. The accelerated model may not be suitable for studying cellular efflux pumps such as P-glycoproteins. However, it is a feasible alternative to the traditional model for rank ordering of compounds in the process of drug discovery and development by significantly improving the turnover time and labor efficiency. This makes it an excellent Caco-2 cell permeability model for high throughput screening. This article was published in J Pharm Sci and referenced in Journal of Bioequivalence & Bioavailability

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