Positive correlation between organic anion transporter 1B function indicated by plasma concentration of coproporphyrin‐I and blood concentration of cyclosporin A in real‐world patients

Aims Cyclosporin A (CyA) has potent inhibitory activity on organic anion transporting polypeptide 1B (OATP1B), causing drug–drug interactions with its substrate drugs. 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropionate (CMPF), a uraemic toxin, has also been suggested to inhibit OATP1B activity. Recent study has identified coproporphyrin‐I (CP‐I) as a specific endogenous substrate for OATP1B, which is useful to indicate OATP1B activity. We investigated the relationship of CP‐I with CyA and CMPF concentrations in patients taking CyA. Methods In total, 121 blood samples from 74 patients who took CyA and underwent routine therapeutic drug monitoring were divided into trough and peak samples. Results CyA and CP‐I concentrations were significantly higher in peak samples than in trough samples. A positive correlation between CP‐I and CyA concentrations was found in all samples and in trough and peak samples, while no correlation was observed between CP‐I and CMPF concentrations. Multiple regression analysis identified CyA and C‐reactive protein concentrations as independent factors affecting CP‐I concentration, with blood CyA concentration having markedly greater contribution to plasma CP‐I concentration. Conclusion The present study suggests that CyA inhibits OATP1B activity in a concentration‐dependent manner in clinical setting, and that dose adjustment of OATP1B substrate drugs coadministered with CyA according to plasma CMPF concentration may not be necessary.