Relationship of hemoglobin level and plasma coproporphyrin‐I concentrations as an endogenous probe for phenotyping OATP1B |
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| Authors: | Yosuke Suzuki Yuri Sasamoto Teruhide Koyama Chisato Yoshijima Ayako Oda Masahiro Nakatochi Michiaki Kubo Yukihide Momozawa Ritei Uehara Keiko Ohno |
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| Affiliation: | 1. Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Kiyose Japan ; 2. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto Japan ; 3. Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya Japan ; 4. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama Japan |
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| Abstract: | Plasma coproporphyrin‐I (CP‐I) concentration is used as a sensitive and selective endogenous probe for phenotyping organic anion transporting polypeptides 1B (OATP1B) activity in many studies. CP‐I is produced in the process of heme synthesis, but the relationship between plasma CP‐I concentrations and heme synthesis activity is unknown. In this study, we evaluated the relationship between plasma CP‐I concentration and hemoglobin level as a biomarker of heme synthesis activity. The data of 391 subjects selected from the Japanese general population were analyzed. One hundred twenty‐six participants had OATP1B1*15 allele, 11 of whom were homozygous (OATP1B1*15/*15). Multiple regression analysis identified hemoglobin level as an independent variable associated with plasma CP‐I concentration (p < 0.0001). A significant positive correlation was observed between hemoglobin level and plasma CP‐I concentration in participants without OATP1B1*15 allele (n = 265; r s = 0.35, p < 0.0001) and with OATP1B1*15 allele (n = 126; r s =0.27, p = 0.0022). However, Kruskal–Wallis test showed no large difference in Kruskal–Wallis statistics between the distribution of plasma CP‐I concentrations and that of ratio of plasma CP‐I to hemoglobin among six OATP1B1 polymorphism groups. These findings suggest that the hemoglobin level seems to reflect biosynthesis of CP‐I. However, correction by hemoglobin level is not required when using basal plasma CP‐I concentration for phenotyping OATP1B activity. Study Highlights - WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
Coproporphyrin‐I (CP‐I) in plasma is a sensitive and specific endogenous biomarker for phenotyping organic anion transporting polypeptides 1B (OATP1B), and has been used for phenotyping OATP1B activity, such as in clinical drug‐drug interaction studies. CP‐I is produced during the process of heme synthesis, indicating that correction of plasma CP‐I concentration by hemoglobin level as an indicator of heme synthesis activity may be needed. - WHAT QUESTION DID THIS STUDY ADDRESS?
Does correction by hemoglobin level improve the usefulness of CP‐I as a probe for OATP1B phenotyping? - WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
Hemoglobin level was identified as an independent variable associated with plasma CP‐I concentrations. However, no large difference in Kruskal–Wallis statistics was observed between the distribution of plasma CP‐I concentrations and that of CP‐I/Hb ratio among six OATP1B1 polymorphism groups. - HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
Hemoglobin level seems to reflect biosynthesis of CP‐I. However, correction by hemoglobin level is not needed when using plasma CP‐I concentration for phenotyping OATP1B activity. |
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