In a directional assay format for assessment of transporter involvement (e.g., substrate potential for an efflux transporter), describe conditions, based on test compound characteristics, that may...

In a directional assay format for assessment of transporter involvement (e.g., substrate potential for an efflux transporter), describe conditions, based on test compound characteristics, that may result in: (a) Exaggerated Efflux Ratio (i.e., False Positives). A: In a BCRP-overexpressing cell line (e.g., BCRPMDCK with residual canine P-gp from the parental cells), a compound that is a substrate of P-gp but not BCRP would look like a positive. (b) Underestimate Efflux Ratio (i.e., False Negatives). A: A compound that requires a basolateral uptake transporter that is not expressed in the test system would look like a negative. What steps can be taken to alleviate these conditions?