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.