Drug Absorption and Distribution Study

Absorption Study (CaCo-2):

Our absorption study model is designed to classify the absorption potential of our customers' compounds. We use Caco-2 cell monolayers to predict intestinal drug absorption. We routinely run assays for our customers that determine active and passive transport of a compound across cell monolayers.

Distribution Study: Cell permeability and efflux assays (MDR1-MDCKII):

The P-gp transporter is an efflux transporter that is encoded by the ABCB1 gene. P-gp is also known as P-glycoprotein and the Multi-Drug Resistance transporter 1 (MDR1). P-gp (MDR1) is expressed in many tissues of the body including in the kidney on the apical side of the intestinal lumen, the apical side of the bile canaliculus in liver hepatocytes, the apical membrane of proximal tubule epithelial cells and the apical side of the capillaries in the blood brain barrier (BBB). P-gp (MDR1) serves to limit the absorption of substrates, protect them from entering the brain and also to mediate their renal and hepatic elimination.

Human P-gp (MDR1) is known to be a determinant of drug absorption, distribution, and excretion of a number of clinically important drugs. P-gp is widely expressed in major organs, and, more specifically, P-gp is highly expressed in the capillaries of the blood brain barrier (BBB) and poses a barrier to brain penetration of its substrates. Given that P-gp efflux liability can be a major hurdle for CNS therapeutic drugs to cross the BBB and reach the target, the interactions of CNS compounds with P-gp may lead to the lack of CNS activity as a result of the decreased brain penetration. Thus, the prediction and understanding of the relevance of P-gp-mediated efflux transport have become important activities in the discovery and development of CNS drugs. Transwell-based assays using polarized MDCKII and MDR1-MDCKII cell lines provide a great tool to classify compounds as P-gp substrates. Comparison of the efflux ratios between MDR1-MDCKII and MDCKII transwell assays can provide a measure of the specific human P-gp-mediated efflux activity.

Apical vs. Basolateral permeability (Caco-2, pH 6.5/7.4)
Apical vs. Basolateral permeability (Caco-2, pH 7.4/7.4)
Apical vs. Basolateral permeability (Caco-2, pH 7.4/7.4 + verapamil)
Apical vs. Basolateral permeability (MDCKII, pH 7.4/7.4)
Apical vs. Basolateral permeability (MDR1-MDCKII, pH 7.4/7.4)
Apical vs. Basolateral permeability (MDR1-MDCKII, pH 7.4/7.4 + verapamil)
Basolateral vs. Apical permeability (Caco-2, pH 6.5/7.4)
Basolateral vs. Apical permeability (Caco-2, pH 7.4/7.4)
Basolateral vs. Apical permeability (Caco-2, pH 7.4/7.4 + verapamil)
Basolateral vs. Apical permeability (MDCKII, pH 7.4/7.4)
Basolateral vs. Apical permeability (MDR1-MDCKII, pH 7.4/7.4)
Basolateral vs. Apical permeability (MDR1-MDCKII, pH 7.4/7.4 + verapamil)

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