Coproporphyrin-I (CP-I)（卟吩原）已被用作有机阴离子转运多肽（OATP）1B的内源性生物标志物。在本研究中，我们确定了在ensitrelvir的鸡尾酒药物相互作用（DDI）研究中的CP-I浓度，以评估OATP1B的抑制潜力，因为在这项研究中，ensitrelvir导致了罗伐他汀浓度的升高，引发了乳腺癌抗蛋白和OATP1B抑制的担忧。此外，在ensitrelvir的首次人体研究（FIH）中，我们比较了活性组和安慰剂组之间的CP-I浓度，以验证在早期药物开发阶段是否能够估计OATP1B的抑制潜力。在鸡尾酒DDI研究中，CP-I在给予ensitrelvir与未给予ensitrelvir时没有差异，表明ensitrelvir没有OATP1B的抑制作用。虽然在FIH研究的治疗组中，个体之间的CP-I浓度有一定的变异性，但通过将CP-I浓度与给药前的值进行归一化，可以减小这些变异性，表明这种归一化方法可以用于比较不同参与者的CP-I浓度。最后，我们得出结论，在FIH研究中，ensitrelvir不会影响CP-I浓度。这些结果表明，在人体中早期评估OATP1B介导的DDI潜力时，CP-I的测定以及其归一化方法是有用的。（版权©2023，由Elsevier Inc.出版）

Coproporphyrin-I (CP-I) has been investigated as an endogenous biomarker of organic anion transporting polypeptide (OATP) 1B. Here, we determined the CP-I concentrations in a cocktail drug-drug interaction (DDI) study of ensitrelvir to evaluate the OATP1B inhibitory potential because ensitrelvir had increased plasma concentrations of rosuvastatin in this study, raising concerns about breast cancer resistance protein and OATP1B inhibition. Furthermore, CP-I concentrations were compared between active and placebo groups in a first-in-human (FIH) study of ensitrelvir to verify whether the OATP1B inhibitory potential could be estimated at an early drug development stage. In the cocktail DDI study, CP-I did not differ between with/without administration of ensitrelvir, indicating that ensitrelvir has no OATP1B inhibitory effect. Although there were some individual variabilities in CP-I concentrations among the treatment groups in the FIH study, the normalization of CP-I concentrations with pre-dose values minimized these variabilities, suggesting that this normalized method would be helpful for comparing the CP-I from different participants. Finally, we concluded that CP-I concentrations were not affected by ensitrelvir in the FIH study. These results suggested that the CP-I determination in an FIH study and its normalized method can be useful for an early evaluation of the OATP1B-mediated DDI potential in humans.Copyright © 2023. Published by Elsevier Inc.