Plasma coproporphyrins for evaluating OATP1B and OATP2B1 activities: Coproporphyrin-III unsuitable as an OATP2B1...

Organic anion transporting polypeptides (OATP)1B1/1B3 are mainly expressed in the liver, whereas OATP2B1 is expressed in the liver as well as in the intestine. Coproporphyrin (CP)-I has been reported to be a highly sensitive biomarker for the OATP family, and its isomer, CP-III, is transported not only by OATP1B1 but also by OATP2B1. Thus, hepatic OATP1B1/1B3 and OATP2B1 activities may be predicted by measuring CP-I and CP-III. We measured plasma CP-I and CP-III concentrations in a sample of Japanese general population and evaluated the relationship between the CP isomers and polymorphisms in the OATP family. In addition, we evaluated the performance of CP-I, CP-III, and CP-I+CP-III (assuming that CP-I and CP-III are not separated) using receiver operating characteristic curves. Plasma CP-I concentration was significantly higher in OATP1B1∗15 carriers (participants with polymorphisms that reduce OATP1B1 activity) than in wild-type OATP1B1 participants (P < .05 for all). Although there was a slight difference in plasma CP-I concentration in OATP2B1 polymorphism, there were no differences in plasma CP-I and CP-III concentrations between groups based on OATP2B1 and OATP1B3 polymorphisms. Also, the area under the receiver operating characteristic curve of CP-I for discriminating OATP1B1∗15 carriers was significantly larger than those of CP-III and CP-I+CP-III (P < .05). In conclusion, plasma CP-III concentration is unsuitable as a hepatic OATP2B1 biomarker. On the other hand, CP-I is a highly sensitive endogenous biomarker for the assessment of OATP1B1 activity, and quantification of CP-I separated from CP-III is desirable for more accurate prediction of OATP1B1 activity. SIGNIFICANCE STATEMENT: Coproporphyrin (CP)-I and CP-III were spotlighted as endogenous biomarkers for evaluating hepatic organic anion transporting polypeptide (OATP) activity. This study evaluates the relationship between the CP isomers and polymorphisms in the OATP family and the performance of CP-I, CP-III, and CP-I+CP-III as an OATP1B1 biomarker. The results indicate that CP-III is unsuitable as a biomarker for the OATP family, while reinforcing the evidence of CP-I as a specific OATP1B1 biomarker, and contributes to more specific evaluation of OATP1B1 activity.