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Factors Influencing Plasma Coproporphyrin‐I Concentration as Biomarker of OATP1B Activity in Patients With Rheumatoid Arthritis
Author(s) -
Ono Hiroyuki,
Tanaka Ryota,
Suzuki Yosuke,
Oda Ayako,
Ozaki Takashi,
Tatsuta Ryosuke,
Maeshima Keisuke,
Ishii Koji,
Ohno Keiko,
Shibata Hirotaka,
Itoh Hiroki
Publication year - 2021
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2375
Subject(s) - rheumatoid arthritis , biomarker , medicine , proinflammatory cytokine , tumor necrosis factor alpha , pharmacology , in vivo , plasma concentration , endocrinology , arthritis , chemistry , immunology , biology , inflammation , biochemistry , microbiology and biotechnology
Organic anion transporting polypeptides (OATPs) 1B are drug transporters mainly expressed in the sinusoidal membrane. In previous reports, genetic factor, 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF), which is one of the uremic toxins, inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) decreased OATP1B1 activity in vitro , but in vivo effects of these factors have not been elucidated. Plasma coproporphyrin‐I (CP‐I) is spotlighted as a highly accurate endogenous substrate of OATP1B. This study focused on patients with rheumatoid arthritis (RA) and evaluated the influence of several factors comprising gene polymorphisms, uremic toxins, and inflammatory cytokines on OATP1B activity using plasma CP‐I concentration. Thirty‐seven outpatients with RA who satisfied the selection criteria were analyzed at the time of recruitment (baseline) and at the next visit. OATP1B1*15 carriers tended to have higher CP‐I concentration compared with noncarriers. Plasma CP‐I correlated positively with CMPF concentration, but did not correlate with IL‐6 or TNF‐α concentration. Multiple logistic regression analysis by stepwise selection identified plasma CMPF concentration and OATP1B1*15 allele as significant factors independently affecting plasma CP‐I concentration at baseline and at the next visit, respectively. In conclusion, the present results suggest that inflammatory cytokines do not have clinically significant effects on OATP1B activity, whereas the effects of genetic polymorphisms and uremic toxins should be considered.