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

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; rs = 0.35, p < 0.0001) and with OATP1B1*15 allele (n = 126; rs =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.

[1]  Sagnik Chatterjee,et al.  Transporter Activity Changes in Nonalcoholic Steatohepatitis: Assessment with Plasma Coproporphyrin I and III , 2020, The Journal of Pharmacology and Experimental Therapeutics.

[2]  M. Kubo,et al.  Substantially Increased Plasma Coproporphyrin‐I Concentrations Associated With OATP1B1*15 Allele in Japanese General Population , 2020, Clinical and translational science.

[3]  H. Kusuhara,et al.  Dose‐Dependent Inhibition of OATP1B by Rifampicin in Healthy Volunteers: Comprehensive Evaluation of Candidate Biomarkers and OATP1B Probe Drugs , 2020, Clinical pharmacology and therapeutics.

[4]  Katya L. Masconi,et al.  Donor Deferral Due to Low Hemoglobin-An Updated Systematic Review. , 2019, Transfusion medicine reviews.

[5]  L. Chinn,et al.  Complex DDI by Fenebrutinib and the Use of Transporter Endogenous Biomarkers to Elucidate the Mechanism of DDI , 2019, Clinical pharmacology and therapeutics.

[6]  Yuichi Sugiyama,et al.  Expanded Physiologically‐Based Pharmacokinetic Model of Rifampicin for Predicting Interactions With Drugs and an Endogenous Biomarker via Complex Mechanisms Including Organic Anion Transporting Polypeptide 1B Induction , 2019, CPT: Pharmacometrics & Systems Pharmacology.

[7]  Kenta Yoshida,et al.  GDC-0810 Pharmacokinetics and Transporter-Mediated Drug Interaction Evaluation with an Endogenous Biomarker in the First-in-Human, Dose Escalation Study , 2019, Drug Metabolism and Disposition.

[8]  H. Itoh,et al.  Recovery of OATP1B Activity after Living Kidney Transplantation in Patients with End-Stage Renal Disease , 2019, Pharmaceutical Research.

[9]  A. D. Rodrigues,et al.  PBPK Modeling of Coproporphyrin I as an Endogenous Biomarker for Drug Interactions Involving Inhibition of Hepatic OATP1B1 and OATP1B3 , 2018, CPT: pharmacometrics & systems pharmacology.

[10]  R. Sane,et al.  Quantitative Prediction of OATP‐Mediated Drug‐Drug Interactions With Model‐Based Analysis of Endogenous Biomarker Kinetics , 2018, CPT: pharmacometrics & systems pharmacology.

[11]  Jiachang Gong,et al.  Further Studies to Support the Use of Coproporphyrin I and III as Novel Clinical Biomarkers for Evaluating the Potential for Organic Anion Transporting Polypeptide 1B1 and OATP1B3 Inhibition , 2018, Drug Metabolism and Disposition.

[12]  M. Monshouwer,et al.  Clinical Investigation of Coproporphyrins as Sensitive Biomarkers to Predict Mild to Strong OATP1B-Mediated Drug–Drug Interactions , 2018, Clinical Pharmacokinetics.

[13]  Kayode Ogungbenro,et al.  Gaining Mechanistic Insight Into Coproporphyrin I as Endogenous Biomarker for OATP1B‐Mediated Drug–Drug Interactions Using Population Pharmacokinetic Modeling and Simulation , 2018, Clinical pharmacology and therapeutics.

[14]  W. Humphreys,et al.  Comparative Evaluation of Plasma Bile Acids, Dehydroepiandrosterone Sulfate, Hexadecanedioate, and Tetradecanedioate with Coproporphyrins I and III as Markers of OATP Inhibition in Healthy Subjects , 2017, Drug Metabolism and Disposition.

[15]  W. Humphreys,et al.  Coproporphyrins in Plasma and Urine Can Be Appropriate Clinical Biomarkers to Recapitulate Drug-Drug Interactions Mediated by Organic Anion Transporting Polypeptide Inhibition , 2016, The Journal of Pharmacology and Experimental Therapeutics.

[16]  M. Eriksson,et al.  Effect of Statin Treatment on Plasma 4β-Hydroxycholesterol Concentrations. , 2016, Basic & clinical pharmacology & toxicology.

[17]  D. Bednarczyk,et al.  Organic anion transporting polypeptide (OATP)-mediated transport of coproporphyrins I and III , 2016, Xenobiotica; the fate of foreign compounds in biological systems.

[18]  W. Humphreys,et al.  Coproporphyrins I and III as Functional Markers of OATP1B Activity: In Vitro and In Vivo Evaluation in Preclinical Species , 2016, The Journal of Pharmacology and Experimental Therapeutics.

[19]  W. Haefeli,et al.  CYP3A activity: towards dose adaptation to the individual , 2016, Expert opinion on drug metabolism & toxicology.

[20]  Y. Masuo,et al.  Increased Plasma Concentrations of Unbound SN-38, the Active Metabolite of Irinotecan, in Cancer Patients with Severe Renal Failure , 2016, Pharmaceutical Research.

[21]  A. Tsubota,et al.  Different Interaction Profiles of Direct-Acting Anti-Hepatitis C Virus Agents with Human Organic Anion Transporting Polypeptides , 2014, Antimicrobial Agents and Chemotherapy.

[22]  S. Fisher,et al.  A systematic review of factors associated with the deferral of donors failing to meet low haemoglobin thresholds , 2013, Transfusion medicine.

[23]  Y. Kanda,et al.  Investigation of the freely available easy-to-use software ‘EZR' for medical statistics , 2012, Bone Marrow Transplantation.

[24]  L. Lesko,et al.  Individualization of Drug Therapy: History, Present State, and Opportunities for the Future , 2012, Clinical pharmacology and therapeutics.

[25]  Y Kumagai,et al.  Identification of the Rate‐Determining Process in the Hepatic Clearance of Atorvastatin in a Clinical Cassette Microdosing Study , 2011, Clinical pharmacology and therapeutics.

[26]  R. Kim,et al.  Hepatic organic anion transporting polypeptide transporter and thyroid hormone receptor interplay determines cholesterol and glucose homeostasis , 2011, Hepatology.

[27]  M. Horio,et al.  Modification of the CKD epidemiology collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[28]  M. Schwab,et al.  Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation , 2008, Analytical and bioanalytical chemistry.

[29]  P. Neuvonen,et al.  Different Effects of SLCO1B1 Polymorphism on the Pharmacokinetics of Atorvastatin and Rosuvastatin , 2007, Clinical pharmacology and therapeutics.

[30]  Mikko Niemi,et al.  SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid , 2006, Pharmacogenetics and genomics.

[31]  Wei Zhang,et al.  Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide. , 2006, British journal of clinical pharmacology.

[32]  R. Lathe,et al.  Porphyrinuria in childhood autistic disorder: implications for environmental toxicity. , 2006, Toxicology and applied pharmacology.

[33]  R. Kim,et al.  Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. , 2006, Gastroenterology.

[34]  Caroline A. Lee,et al.  Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment , 2005, Clinical pharmacology and therapeutics.

[35]  D. Oh,et al.  Effect of OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteers , 2005, Clinical pharmacology and therapeutics.

[36]  Y Vanrenterghem,et al.  Combined Therapy with Atorvastatin and Calcineurin Inhibitors: No Interactions with Tacrolimus , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[37]  Kaoru Kobayashi,et al.  Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells , 2005, Pharmacogenetics and genomics.

[38]  Y. Sugiyama,et al.  Functional analysis of single nucleotide polymorphisms of hepatic organic anion transporter OATP1B1 (OATP-C). , 2004, Pharmacogenetics.

[39]  Y. Kasuya,et al.  Evidence for the validity of cortisol 6 beta-hydroxylation clearance as a new index for in vivo cytochrome P450 3A phenotyping in humans. , 2003, Drug metabolism and disposition: the biological fate of chemicals.

[40]  Yuichi Sugiyama,et al.  Polymorphisms of OATP‐C (SLC21A6) and OAT3 (SLC22A8) genes: Consequences for pravastatin pharmacokinetics , 2003, Clinical pharmacology and therapeutics.

[41]  L. Bertilsson,et al.  Antiepileptic drugs increase plasma levels of 4beta-hydroxycholesterol in humans: evidence for involvement of cytochrome p450 3A4. , 2001, The Journal of biological chemistry.

[42]  D. Jorkasky,et al.  Urinary excretion of 6β‐hydroxycortisol as an in vivo marker for CYP3A induction: Applications and recommendations , 1998, Clinical pharmacology and therapeutics.

[43]  Y. Komiyama,et al.  Cloning and characterization of K562 cells on hemoglobin synthetic activity. , 1993, Biological and Pharmaceutical Bulletin.

[44]  N. Nakamichi,et al.  Direct Inhibition and Down-regulation by Uremic Plasma Components of Hepatic Uptake Transporter for SN-38, an Active Metabolite of Irinotecan, in Humans , 2013, Pharmaceutical Research.

[45]  G. Chalevelakis,et al.  Adverse effect of cis-diamminedichloroplatinum II (CDDP) on porphyrin metabolism in man , 2004, Cancer Chemotherapy and Pharmacology.