We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
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.
- Authors
Watanabe, Takuma; Tanaka, Ryota; Suzuki, Yosuke; Sato, Haruki; Negami, Jun; Yoshijima, Chisato; Oda, Ayako; Ono, Hiroyuki; Tatsuta, Ryosuke; Ohno, Keiko; Itoh, Hiroki
- Abstract
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.
- Subjects
ORGANIC anion transporters; CYCLOSPORINE; DRUG monitoring; MULTIPLE regression analysis; DRUG interactions; C-reactive protein
- Publication
British Journal of Clinical Pharmacology, 2023, Vol 89, Issue 5, p1672
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/bcp.15640