Factors Influencing Plasma Coproporphyrin-I Concentration as Biomarker of OATP1B Activity in Patients With Rheumatoid Arthritis.

Abstract

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.

• Authors: Hiroyuki Ono, Ryota Tanaka, Yosuke Suzuki, Ayako Oda, Takashi Ozaki, Ryosuke Tatsuta, Keisuke Maeshima, Koji Ishii, Keiko Ohno, Hirotaka Shibata, Hiroki Itoh
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 110 Issue 4 Pg. 1096-1105 (10 2021) ISSN: 1532-6535 [Electronic] United States
• PMID: 34319605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.

Chemical References

• 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid
• Biomarkers
• Coproporphyrins
• Furans
• Interleukin-6
• Liver-Specific Organic Anion Transporter 1
• Propionates
• SLCO1B1 protein, human
• Tumor Necrosis Factor-alpha
• coproporphyrin I

Topics

• Aged
• Arthritis, Rheumatoid (metabolism)
• Biomarkers (blood)
• Coproporphyrins (blood)
• Female
• Furans (metabolism)
• Humans
• Interleukin-6 (metabolism)
• Liver-Specific Organic Anion Transporter 1 (genetics)
• Male
• Middle Aged
• Pharmacogenomic Variants
• Propionates (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)