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

Suzuki, Yosuke; Sasamoto, Yuri; Koyama, Teruhide; Yoshijima, Chisato; Oda, Ayako; Nakatochi, Masahiro; Kubo, Michiaki; Momozawa, Yukihide; Uehara, Ritei; Ohno, Keiko

doi:10.1111/cts.12996

Cited by 5 publications

(4 citation statements)

References 49 publications

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“…In all patients, the male to female ratio was 40 to 34, and the most frequent underlying disease was nephrotic syndrome, followed by organ transplanta- 1121.6 ng/mL, respectively. CP-I concentration in patients taking CyA was higher than that in healthy volunteers (0.48 ± 0.17 ng/mL) reported by Suzuki et al 23 Median CP-I concentrations in patients with nephrotic syndrome, organ transplantation, and aplastic anaemia or pure red-cell aplasia were 1.19, 1.17 and 1.02 ng/mL, respectively, suggesting no difference among underlying diseases. The concentrations of CyA and CP-I were significantly higher in peak samples than in trough samples (CyA: P < .001, CP-I: P < .001), while CMPF concentration did not differ between the 2 groups.…”

Section: Patient Characteristicscontrasting

confidence: 52%

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

Watanabe

Tanaka

Suzuki

et al. 2022

Brit J Clinical Pharma

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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.

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Section: Patient Characteristicscontrasting

confidence: 52%

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

Watanabe

Tanaka

Suzuki

et al. 2022

Brit J Clinical Pharma

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“… 22 , 39 In one study, blood hemoglobin level was associated with plasma CPI levels, but no independent association between hemoglobin and CPI concentrations was found after adjusting for sex. 39 Similarly, in our study, blood hemoglobin concentration showed no independent association with CPI or CPIII concentration in the final linear regression model including sex as an independent variable. On the other hand, the concentrations of some other endogenous OATP1B1 substrates have also shown similar sex‐related differences.…”

Section: Discussionmentioning

confidence: 98%

“…Consistent with previous data regarding CPI, 22 we saw on average 30% higher plasma CPI and CPIII concentrations in men than in women. These sex‐related differences in plasma CP levels have been suggested to be at least partly due to a higher heme synthesis rate in men 22,39 . In one study, blood hemoglobin level was associated with plasma CPI levels, but no independent association between hemoglobin and CPI concentrations was found after adjusting for sex 39 .…”

Section: Discussionmentioning

confidence: 99%

“…These sex‐related differences in plasma CP levels have been suggested to be at least partly due to a higher heme synthesis rate in men 22,39 . In one study, blood hemoglobin level was associated with plasma CPI levels, but no independent association between hemoglobin and CPI concentrations was found after adjusting for sex 39 . Similarly, in our study, blood hemoglobin concentration showed no independent association with CPI or CPIII concentration in the final linear regression model including sex as an independent variable.…”

Section: Discussionmentioning

confidence: 99%

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Performance of Plasma Coproporphyrin I and III as OATP1B1 Biomarkers in Humans

Neuvonen

Tornio

Hirvensalo

et al. 2021

Clin Pharma and Therapeutics

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Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Coproporphyrin I (CPI) and coproporphyrin III (CPIII) are promising biomarkers to measure organic anion transporting polypeptide (OATP) 1B activity in humans. In vitro data suggest that CPI and CPIII are better substrates for OATP1B1 than for OATP1B3. WHAT QUESTION DID THIS STUDY ADDRESS? Are CPI and CPIII sensitive OATP1B1 biomarkers in humans? What is the performance of CPI and CPIII compared with the highly specific and sensitive OATP1B1 endogenous probes glycochenodeoxycholate 3-O-glucuronide (GCDCA-3G) and glycodeoxycholate 3-O-glucuronide (GDCA-3G)?WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? CPI clearly outperformed CPIII in distinguishing the genetically poor, decreased, increased, and highly increased OATP1B1 function groups, indicating higher sensitivity as an OATP1B1 biomarker. However, GCDCA-3G showed an even better sensitivity than CPI. Careful standardization of plasma CP handling and storing is needed for reliable quantification. HOW MIGHT THIS CHANGE CLINICAL PHARMA-COLOGY OR TRANSLATIONAL SCIENCE?  CPI may be a useful endogenous probe substrate along with the more sensitive GCDCA-3G for measuring OATP1B1 activity during drug development and in clinical practice.

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Characterization of endogenous markers of hepatic function in patients receiving itraconazole treatment for prophylaxis of deep mycosis

Nakatsugawa

Naito

Imoto

et al. 2023

Journal of Infection and Chemotherapy

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

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 5 publications

References 49 publications

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

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

Performance of Plasma Coproporphyrin I and III as OATP1B1 Biomarkers in Humans

Characterization of endogenous markers of hepatic function in patients receiving itraconazole treatment for prophylaxis of deep mycosis

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