Simultaneous quantification of coproporphyrin-I and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid in human plasma using ultra-high performance liquid chromatography coupled to tandem mass spectrometry

Clinical Translational Sci

Sasamoto

Koyama

et al. 2020

Self Cite

Coproporphyrin-I (CP-I) in plasma is a sensitive and specific endogenous probe for phenotyping organic anion transporting polypeptides 1B (OATP1B, encoded by SLCO1B). A few small-scale studies suggested that plasma CP-I concentration is affected by OATP1B1 polymorphism, but detailed studies are lacking. In this large-scale study, we measured plasma CP-I concentrations in 391 subjects from the Japanese general population, and evaluated the relationship between plasma CP-I concentrations and OATP1B1 polymorphisms to further assess the utility of plasma CP-I concentrations as an endogenous OATP1B probe. Plasma CP-I concentrations were 0.45 ± 0.12, 0.47 ± 0.16, 0.47 ± 0.20, 0.50 ± 0.15, 0.54 ± 0.14, and 0.74 ± 0.31 ng/mL in participants with OATP1B1*1b/*1b (n = 103), *1a/*1b (n = 122), *1a/*1a (n = 40), *1b/*15 (n = 74), *1a/*15 (n = 41), and *15/*15 (n = 11), respectively, showing an ascending rank order with significant difference (P < 0.0001). Post hoc analysis revealed significant increases in plasma CP-I concentration in OATP1B1*1b/*15 (P = 0.036), *1a/*15 (P = 0.0005), and *15/*15 (P = 0.0003) groups compared with the OATP1B1*1b/*1b group. There was no significant difference among OATP1B genotypes in plasma concentration of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, a uremic toxin reported to decrease OATP1B activity in vivo. These findings confirm the utility of plasma CP-I concentrations as an endogenous biomarker for phenotyping of OATP1B activity. Plasma CP-I concentration is potentially useful for the study of drug-drug interactions via OATP1B or individual dose adjustment of OATP1B substrates. Drug transporters are localized at cell membranes and involved in drug transport in various tissues such as the liver, kidneys, gastrointestinal tract, and brain endothelium. Organic anion transporting polypeptides 1B (OATP1B, encoded by SLCO1B) is a hepatic uptake transporter that substantially affect pharmacokinetics of some drugs, such as hydroxymethylglutaryl (HMG)-CoA reductase inhibitors and some anti-hepatitis C virus drugs. 1-6 In vivo OATP1B activity has large interindividual variability and is affected by environmental, physiologic, and genetic factors. For example, OATP inhibitors, such as rifampicin and cyclosporin A, inhibit OATP1B activity and increase plasma concentrations

Section: Discussionsupporting

confidence: 87%

“…Plasma concentrations of CP‐I and CMPF were measured simultaneously using an ultra‐high performance liquid chromatography coupled to tandem mass spectrometry according to the procedures that we reported previously 36 . Inter‐assay and intra‐assay accuracy and precision were < 7.6% for CP‐I and < 4.1% for CMPF.…”

Section: Methodsmentioning

confidence: 99%

Substantially Increased Plasma Coproporphyrin‐I Concentrations Associated With OATP1B115* Allele in Japanese General Population

Clinical Translational Sci

Sasamoto

Koyama

et al. 2020

Self Cite

“…Plasma CP‐I concentration was measured using ultra‐high performance liquid chromatography coupled to tandem mass spectrometry according to the procedures that we reported previously 14 . Inter‐ and intra‐assay accuracy was 92.1%–110.2% and 96.7%–100.6%, respectively, and precision was less than 7.6% and less than 6.8%.…”

Section: Methodsmentioning

confidence: 99%

“… 9 , 10 As a physiologic factor, 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid accumulation due to chronic kidney failure has recently been reported to decrease OATP1B activity. 11 , 12 , 13 , 14 As genetic factors, SLCO1B1 exhibits two major single nucleotide polymorphisms: A388G and T521C. These polymorphisms form four haplotypes: OATP1B1*1a (c.388A‐c.521 T), OATP1B1*1b (c.388G‐c.521 T), OATP1B1*5 (c.388A‐c.521C), and OATP1B1*15 (c.388G‐c.521C).…”

Section: Introductionmentioning

confidence: 99%

“…For example, OATP inhibitors, such as rifampicin and cyclosporin A, inhibit OATP1B activity and increase plasma concentrations of OATP1B substrates 9,10 . As a physiologic factor, 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid accumulation due to chronic kidney failure has recently been reported to decrease OATP1B activity 11–14 . As genetic factors, SLCO1B1 exhibits two major single nucleotide polymorphisms: A388G and T521C.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship of hemoglobin level and plasma coproporphyrin‐I concentrations as an endogenous probe for phenotyping OATP1B

Clinical Translational Sci

Sasamoto

Koyama

et al. 2021

Self Cite

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

Ono

Tanaka

Clin Pharma and Therapeutics

et al. 2021

Self Cite

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.