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A previous study in 356 healthy Finnish volunteers showed that glycochenodeoxycholate 3‐O‐glucuronide (GCDCA‐3G) and glycodeoxycholate 3‐O‐glucuronide (GDCA‐3G) are promising biomarkers of organic anion transporting polypeptide 1B1 (OATP1B1). In the same cohort, we now evaluated the performances of two other OATP1B1 biomarkers, coproporphyrin I (CPI) and III (CPIII), and compared them with GCDCA‐3G and GDCA‐3G. Based on decreased ( *5  and  *15 ) and increased ( *14  and  *20 ) function  SLCO1B1  haplotypes, we stratified the participants to poor, decreased, normal, increased, and highly increased OATP1B1 function groups. Fasting plasma CPI concentration was 68% higher in the poor (95% confidence interval, 44%, 97%;  P  = 1.74 × 10 −10 ), 7% higher in the decreased (0%, 15%;  P  = 0.0385), 10% lower in the increased (3%, 18%;  P  = 0.0087), and 23% lower in the highly increased (1%, 40%;  P  = 0.0387) function group than in the normal function group. CPIII concentration was 27% higher (7%, 51%;  P  = 0.0071) in the poor function group than in the normal function group. CPI and CPIII detected poor OATP1B1 function with areas under the precision‐recall curve (AUPRC) of 0.388 (95% confidence interval, 0.197, 0.689) and 0.0798 (0.0485, 0.203), and receiver operating characteristic curve (AUROC) of 0.888 (0.851, 0.919) and 0.731 (0.682, 0.776). The AUPRC and AUROC of GCDCA‐3G were, however, 0.389 (0.258, 0.563) and 0.100 (−0.0046, 0.204;  P  = 0.0610) larger than those of CPI, and 0.697 (0.555, 0.831) and 0.257 (0.141, 0.373;  P  < 0.0001) larger than those of CPIII. In conclusion, these data indicate that plasma CPI outperforms CPIII in detecting altered OATP1B1 function, but GCDCA‐3G is an even more sensitive OATP1B1 biomarker than CPI.

Performance of Plasma Coproporphyrin I and III as OATP1B1 Biomarkers in Humans