Kinzi Jonny, Grube Markus, Hussner Janine, Seibert Isabell, Hamburger Matthias, Meyer Zu Schwabedissen Henriette E
Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Center of Drug Absorption and Transport, Institute for Pharmacology, University Medicine Greifswald, Felix-Hausdorff-Str. 3, 17487 Greifswald, Germany.
J Pharmacol Sci. 2023 Nov;153(3):170-174. doi: 10.1016/j.jphs.2023.09.003. Epub 2023 Sep 14.
Coproporphyrin I (CPI) and III (CPIII) are discussed as biomarkers for organic anion transporting polypeptides (OATPs). We report on CPI and CPIII levels in wildtype, rSlco2b1-knockout, and SLCO2B1-humanized rats at baseline and after administration of atorvastatin, an inhibitor of the CPIII-specific rOATP2B1/hOATP2B1 and the CPI/CPIII-transporting rOATP1B2. OATP-inhibition by atorvastatin leads to significantly increased CPI and CPIII serum levels. However, basal CP serum levels in rSlco2b1-knockout animals were significantly lower (CPI), or unaffected (CPIII). In the presence of atorvastatin, this genotype effect was abolished. In conclusion, our results indicate an unexpected impact of OATP2B1 on CP serum levels in rats.
粪卟啉I（CPI）和III（CPIII）被作为有机阴离子转运多肽（OATP）的生物标志物进行讨论。我们报告了野生型、rSlco2b1基因敲除型和SLCO2B1人源化大鼠在基线时以及给予阿托伐他汀（一种CPIII特异性rOATP2B1/hOATP2B1和转运CPI/CPIII的rOATP1B2的抑制剂）后的CPI和CPIII水平。阿托伐他汀对OATP的抑制导致CPI和CPIII血清水平显著升高。然而，rSlco2b1基因敲除动物的基础CP血清水平显著降低（CPI）或未受影响（CPIII）。在存在阿托伐他汀的情况下，这种基因型效应被消除。总之，我们的结果表明OATP2B1对大鼠CP血清水平有意外影响。
