Figure 4.

Combined interaction of drugs and kynurenic acid (KA) on OAT1-mediated fluorescein uptake. (A) Schematic representation of the co-incubation of fluorescein with variable concentrations of drugs and fixed concentration of KA. (B) The drug alone (grey line) shows a concentration-dependent inhibitory effect that is not affected by the presence of KA (1 µM, green line) in the case of furosemide and statins. For ARBs, the inhibitory effect of the drugs is diminished in the presence of KA. All data are expressed as mean ± SD of four independent experiments. Curves were obtained after non-linear regression analysis. The reference value for the drug alone is fluorescein without the drug (100%), while for the co-incubation with KA the reference value is fluorescein in the presence of KA without the drug (88.2 ± 8.5). Grey regions indicate the therapeutic window of the respective drug.