Drug Metabolizing Enzymes and ABC Transporter

In the small intestine, ABCBl and CYP3A4 form a cooperative barrier against the 

Drug Substrate for Efflux ratio Extraction ratio (%) SD  

A to B ratio apical to basolateral B to A ratio basolateral to apical. Intracellular drug amounts (picomole) are shown in parentheses. Cyclosporin is a known CYP3A4 and ABCBl substrate and inhibitor. GG918 is a specific ABCBl inhibitor. 

Caco-2 cells, all four compounds were significantly metabolized. As expected, addition of the CYP3A inhibitor cyclosporin significantly inhibited the extraction ratios for all drugs. Surprisingly, the decrease in the extraction ratio for midazolam and felodipine, which are not substrates for ABCBl, was 46-60% while these values for the CYP3A and ABCBl substrates K77 and sirolimus were found to be 74—83%. 

An interplay between metabolic enzymes may also occur with uptake transporters 

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Borlak, J. and Zwadlo, C., Expression of drug-metabolizing enzymes, nuclear transcription factors and ABC transporters in Caco-2 cells, Xenobiotica, 33, 927, 2005. 

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