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Review Article| Volume 5, ISSUE 1, P109-118, November 2022

SLCO1B1 Pharmacogenetics in Pediatrics

  • Laura B. Ramsey
    Affiliations
    Division of Clinical Pharmacology, Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Division of Research in Patient Services, Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • Jason A. Sprowl
    Affiliations
    Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA
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  • J. Steven Leeder
    Affiliations
    Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Kansas City, MO, USA

    Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA
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  • Jonathan B. Wagner
    Correspondence
    Corresponding author. Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Kansas City, MO.
    Affiliations
    Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Kansas City, MO, USA

    Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA

    Ward Family Heart Center, Children’s Mercy, Kansas City, MO, USA
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Published:September 28, 2022DOI:https://doi.org/10.1016/j.yamp.2022.05.003

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      References

        • Gaedigk A.
        • Whirl-Carrillo M.
        • Pratt V.M.
        • et al.
        PharmVar and the Landscape of Pharmacogenetic Resources.
        Clin Pharmacol Ther. 2020; 107: 43-46
        • Caudle K.E.
        • Dunnenberger H.M.
        • Freimuth R.R.
        • et al.
        Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC).
        Genet Med. 2017; 19: 215-223
        • van de Steeg E.
        • Stranecky V.
        • Hartmannova H.
        • et al.
        Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver.
        J Clin Invest. 2012; 122: 519-528
        • Cooper-DeHoff R.M.
        • Niemi M.
        • Ramsey L.B.
        • et al.
        The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.
        Clin Pharmacol Ther. 2022; https://doi.org/10.1002/cpt.2557
        • Keppler D.
        The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia.
        Drug Metab Dispos. 2014; 42: 561-565
        • Watchko J.F.
        • Lin Z.
        • Clark R.H.
        • et al.
        Complex multifactorial nature of significant hyperbilirubinemia in neonates.
        Pediatrics. 2009; 124: e868-e877
        • Muller F.
        • Sharma A.
        • Konig J.
        • et al.
        Biomarkers for In Vivo Assessment of Transporter Function.
        Pharmacol Rev. 2018; 70: 246-277
        • Remer T.
        • Boye K.R.
        • Hartmann M.F.
        • et al.
        Urinary markers of adrenarche: reference values in healthy subjects, aged 3-18 years.
        J Clin Endocrinol Metab. 2005; 90: 2015-2021
        • van Groen B.D.
        • van de Steeg E.
        • Mooij M.G.
        • et al.
        Proteomics of human liver membrane transporters: a focus on fetuses and newborn infants.
        Eur J Pharm Sci. 2018; 124: 217-227
        • Prasad B.
        • Gaedigk A.
        • Vrana M.
        • et al.
        Ontogeny of Hepatic Drug Transporters as Quantified by LC-MS/MS Proteomics.
        Clin Pharmacol Ther. 2016; 100: 362-370
        • van Groen B.D.
        • Bi C.
        • Gaedigk R.
        • et al.
        Alternative Splicing of the SLCO1B1 Gene: An Exploratory Analysis of Isoform Diversity in Pediatric Liver.
        Clin Transl Sci. 2020; 13: 509-519
        • Shen H.
        • Dai J.
        • Liu T.
        • et al.
        Coproporphyrins I and III as Functional Markers of OATP1B Activity: In Vitro and In Vivo Evaluation in Preclinical Species.
        J Pharmacol Exp Ther. 2016; 357: 382-393
        • Lai Y.
        • Mandlekar S.
        • Shen H.
        • et al.
        Coproporphyrins in Plasma and Urine Can Be Appropriate Clinical Biomarkers to Recapitulate Drug-Drug Interactions Mediated by Organic Anion Transporting Polypeptide Inhibition.
        J Pharmacol Exp Ther. 2016; 358: 397-404
        • Barnett S.
        • Ogungbenro K.
        • Menochet K.
        • et al.
        Gaining Mechanistic Insight Into Coproporphyrin I as Endogenous Biomarker for OATP1B-Mediated Drug-Drug Interactions Using Population Pharmacokinetic Modeling and Simulation.
        Clin Pharmacol Ther. 2018; 104: 564-574
        • Kaplowitz N.
        • Javitt N.
        • Kappas A.
        Coproporphyrin I and 3 excretion in bile and urine.
        J Clin Invest. 1972; 51: 2895-2899
        • Kameyama Y.
        • Yamashita K.
        • Kobayashi K.
        • 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.
        Pharmacogenet Genomics. 2005; 15: 513-522
        • Wagner J.B.
        • Ruggiero M.
        • Leeder J.S.
        • et al.
        Functional Consequences of Pravastatin Isomerization on OATP1B1-Mediated Transport.
        Drug Metab Dispos. 2020; 48: 1192-1198
        • Niemi M.
        • Schaeffeler E.
        • Lang T.
        • et al.
        High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1).
        Pharmacogenetics. 2004; 14: 429-440
        • Wagner J.B.
        • Abdel-Rahman S.
        • Gaedigk R.
        • et al.
        Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia.
        Clin Pharmacol Ther. 2019; 105: 1501-1512
        • Wagner J.B.
        • Abdel-Rahman S.
        • Van Haandel L.
        • et al.
        Impact of SLCO1B1 Genotype on Pediatric Simvastatin Acid Pharmacokinetics.
        J Clin Pharmacol. 2018; https://doi.org/10.1002/jcph.1080
        • Pasanen M.K.
        • Neuvonen M.
        • Neuvonen P.J.
        • et al.
        SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid.
        Pharmacogenet Genomics. 2006; 16: 873-879
        • Wagner J.B.
        • Abdel-Rahman S.
        • Gaedigk A.
        • et al.
        Impact of SLCO1B1 genetic variation on rosuvastatin systemic exposure in pediatric hypercholesterolemia.
        Clin Transl Sci. 2020; https://doi.org/10.1111/cts.12749
        • Pasanen M.K.
        • Fredrikson H.
        • Neuvonen P.J.
        • et al.
        Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin.
        Clin Pharmacol Ther. 2007; 82: 726-733
        • Yee S.W.
        • Giacomini M.M.
        • Shen H.
        • et al.
        Organic Anion Transporter Polypeptide 1B1 Polymorphism Modulates the Extent of Drug-Drug Interaction and Associated Biomarker Levels in Healthy Volunteers.
        Clin Transl Sci. 2019; 12: 388-399
        • Mori D.
        • Kashihara Y.
        • Yoshikado T.
        • et al.
        Effect of OATP1B1 genotypes on plasma concentrations of endogenous OATP1B1 substrates and drugs, and their association in healthy volunteers.
        Drug Metab Pharmacokinet. 2019; 34: 78-86
        • Wagner J.B.
        • Leeder J.S.
        • Ogungbenro K.
        • et al.
        Effect of SLCO1B1 Genotype on Endogenous Biomarker Coproporhyrin I Baseline in Children and Adolescents.
        Clin Phamacol Ther. 2020; 107: S106-S107
        • Wagner J.B.
        • Leeder J.S.
        • Ogungbenro K.
        • et al.
        Utility of Coproprophyrin I to Predict Statin Exposure in Children and Adolescents.
        Clin Pharmacol Ther. 2021; 2021: 109https://doi.org/10.1002/cpt.2167
        • Neuvonen M.
        • Hirvensalo P.
        • Tornio A.
        • et al.
        Identification of Glycochenodeoxycholate 3-O-Glucuronide and Glycodeoxycholate 3-O-Glucuronide as Highly Sensitive and Specific OATP1B1 Biomarkers.
        Clin Pharmacol Ther. 2021; 109: 646-657
        • Neuvonen M.
        • Tornio A.
        • Hirvensalo P.
        • et al.
        Performance of Plasma Coproporphyrin I and III as OATP1B1 Biomarkers in Humans.
        Clin Pharmacol Ther. 2021; 110: 1622-1632
        • Yee S.W.
        • Giacomini M.M.
        • Hsueh C.H.
        • et al.
        Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.
        Clin Pharmacol Ther. 2016; 100: 524-536
        • Li Y.
        • Talebi Z.
        • Chen X.
        • et al.
        Endogenous Biomarkers for SLC Transporter-Mediated Drug-Drug Interaction Evaluation.
        Molecules. 2021; 26https://doi.org/10.3390/molecules26185500
        • Darwich A.S.
        • Ogungbenro K.
        • Vinks A.A.
        • et al.
        Why has model-informed precision dosing not yet become common clinical reality? lessons from the past and a roadmap for the future.
        Clin Pharmacol Ther. 2017; 101: 646-656
        • McLaughlin M.J.
        • Wagner J.
        • Shahknovich V.
        • et al.
        Considerations for Implementing Precision Therapeutics for Children.
        Clin Transl Sci. 2019; 12: 140-150
        • Wagner J.
        • Abdel-Rahman S.M.
        Pediatric Statin Administration: Navigating a Frontier with Limited Data.
        J Pediatr Pharmacol Ther. 2016; 21: 380-403
        • Baigent C.
        • Keech A.
        • Kearney P.M.
        • et al.
        Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
        Lancet. 2005; 366: 1267-1278
        • Mills E.J.
        • Wu P.
        • Chong G.
        • et al.
        Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials.
        QJM. 2011; 104: 109-124
        • Tonelli M.
        • Lloyd A.
        • Clement F.
        • et al.
        Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis.
        CMAJ. 2011; 183: E1189-E1202
        • O'Gorman C.S.
        • Higgins M.F.
        • O'Neill M.B.
        Systematic review and metaanalysis of statins for heterozygous familial hypercholesterolemia in children: evaluation of cholesterol changes and side effects.
        Pediatr Cardiol. 2009; 30: 482-489
        • Voora D.
        • Shah S.H.
        • Spasojevic I.
        • et al.
        The SLCO1B1∗5 genetic variant is associated with statin-induced side effects.
        J Am Coll Cardiol. 2009; 54: 1609-1616
        • Group S.C.
        • Link E.
        • Parish S.
        • et al.
        SLCO1B1 variants and statin-induced myopathy--a genomewide study.
        N Engl J Med. 2008; 359: 789-799
        • Donnelly L.A.
        • Doney A.S.
        • Tavendale R.
        • et al.
        Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study.
        Clin Pharmacol Ther. 2011; 89: 210-216
        • Fisher C.D.
        • Lickteig A.J.
        • Augustine L.M.
        • et al.
        Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats.
        Eur J Pharmacol. 2009; 613: 119-127
        • Lake A.D.
        • Novak P.
        • Fisher C.D.
        • et al.
        Analysis of global and absorption, distribution, metabolism, and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease.
        Drug Metab Dispos. 2011; 39: 1954-1960
        • Clarke J.D.
        • Hardwick R.N.
        • Lake A.D.
        • et al.
        Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression.
        J Pharmacol Exp Ther. 2014; 348: 452-458
        • Clarke J.D.
        • Novak P.
        • Lake A.D.
        • et al.
        Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease.
        Liver Int. 2017; 37: 1074-1081
        • Taylor Z.L.
        • Vang J.
        • Lopez-Lopez E.
        • et al.
        Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies.
        Cancers (Basel). 2021; 13https://doi.org/10.3390/cancers13112837
        • Trevino L.R.
        • Shimasaki N.
        • Yang W.
        • et al.
        Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects.
        J Clin Oncol. 2009; 27: 5972-5978
        • Cheng Y.
        • Chen M.H.
        • Zhuang Q.
        • et al.
        Genetic factors involved in delayed methotrexate elimination in children with acute lymphoblastic leukemia.
        Pediatr Blood Cancer. 2021; 68: e28858
        • Ramsey L.B.
        • Bruun G.H.
        • Yang W.
        • et al.
        Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition.
        Genome Res. 2012; 22: 1-8
        • Mehta R.S.
        • Taylor Z.L.
        • Martin L.J.
        • et al.
        SLCO1B1 ∗15 allele is associated with methotrexate-induced nausea in pediatric patients with inflammatory bowel disease.
        Clin Transl Sci. 2022; 15: 63-69
        • Kyvsgaard N.
        • Mikkelsen T.S.
        • Als T.D.
        • et al.
        Single nucleotide polymorphisms associated with methotrexate-induced nausea in juvenile idiopathic arthritis.
        Pediatr Rheumatol Online J. 2021; 19: 51
        • Roszkiewicz J.
        • Michalek D.
        • Ryk A.
        • et al.
        SLCO1B1 variants as predictors of methotrexate-related toxicity in children with juvenile idiopathic arthritis.
        Scand J Rheumatol. 2021; 50: 213-217
        • Ramsey L.B.
        • Moncrieffe H.
        • Smith C.N.
        • et al.
        Association of SLCO1B1 ∗14 Allele with Poor Response to Methotrexate in Juvenile Idiopathic Arthritis Patients.
        ACR Open Rheumatol. 2019; 1: 58-62
        • Takahashi K.
        • Nakamura H.
        • Watanabe A.
        • et al.
        Polymorphism in Organic Anion-Transporting Polypeptide Gene Related to Methotrexate Response in Rheumatoid Arthritis Treatment.
        J Nippon Med Sch. 2019; 86: 149-158
        • Arora A.
        • Scholar E.M.
        Role of tyrosine kinase inhibitors in cancer therapy.
        J Pharmacol Exp Ther. 2005; 315: 971-979
        • Sato T.
        • Ito H.
        • Hirata A.
        • et al.
        Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3 and OATP2B1: gefitinib shows contradictory interaction with OATP1B3.
        Xenobiotica. 2018; 48: 73-78
        • Ogasawara K.
        • Wood-Horrall R.N.
        • Thomas M.
        • et al.
        Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach.
        Cancer Chemother Pharmacol. 2021; 88: 941-952
        • Chang M.
        • Bathena S.
        • Christopher L.J.
        • et al.
        Prediction of drug-drug interaction potential mediated by transporters between dasatinib and metformin, pravastatin, and rosuvastatin using physiologically based pharmacokinetic modeling.
        Cancer Chemother Pharmacol. 2022; 89: 383-392
        • Pahwa S.
        • Alam K.
        • Crowe A.
        • et al.
        Pretreatment With Rifampicin and Tyrosine Kinase Inhibitor Dasatinib Potentiates the Inhibitory Effects Toward OATP1B1- and OATP1B3-Mediated Transport.
        J Pharm Sci. 2017; 106: 2123-2135
        • Farasyn T.
        • Pahwa S.
        • Xu C.
        • et al.
        Pre-incubation with OATP1B1 and OATP1B3 inhibitors potentiates inhibitory effects in physiologically relevant sandwich-cultured primary human hepatocytes.
        Eur J Pharm Sci. 2021; 165: 105951
        • Ramsey L.B.
        • Mizuno T.
        • Vinks A.A.
        • et al.
        Delayed methotrexate clearance in patients with acute lymphoblastic leukemia concurrently receiving dasatinib.
        Pediatr Blood Cancer. 2019; 66: e27618
        • Logue J.M.
        • Kiani B.
        • Bitting R.L.
        Pazopanib and Statin-Induced Rhabdomyolysis.
        Case Rep Oncol. 2017; 10: 954-957
        • Kendra K.L.
        • Plummer R.
        • Salgia R.
        • et al.
        A multicenter phase I study of pazopanib in combination with paclitaxel in first-line treatment of patients with advanced solid tumors.
        Mol Cancer Ther. 2015; 14: 461-469
        • Awada A.
        • Hendlisz A.
        • Christensen O.
        • et al.
        Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours.
        Eur J Cancer. 2012; 48: 465-474
      1. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. (Accessed April 20, 2022).

        • Koide H.
        • Tsujimoto M.
        • Takeuchi A.
        • et al.
        Substrate-dependent effects of molecular-targeted anticancer agents on activity of organic anion transporting polypeptide 1B1.
        Xenobiotica. 2018; 48: 1059-1071
        • Hu S.
        • Mathijssen R.H.
        • de Bruijn P.
        • et al.
        Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations.
        Br J Cancer. 2014; 110: 894-898
        • Leblanc A.F.
        • Sprowl J.A.
        • Alberti P.
        • et al.
        OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity.
        J Clin Invest. 2018; 128: 816-825
        • Hayden E.R.
        • Chen M.
        • Pasquariello K.Z.
        • et al.
        Regulation of OATP1B1 Function by Tyrosine Kinase-mediated Phosphorylation.
        Clin Cancer Res. 2021; 27: 4301-4310
        • Khurana V.
        • Minocha M.
        • Pal D.
        • et al.
        Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors.
        Drug Metabol Drug Interact. 2014; 29: 249-259
        • de Ferranti S.D.
        • Rodday A.M.
        • Parsons S.K.
        • et al.
        Cholesterol Screening and Treatment Practices and Preferences: A Survey of United States Pediatricians.
        J Pediatr. 2017; 185: 99-105 e2
        • Dixon D.B.
        • Kornblum A.P.
        • Steffen L.M.
        • et al.
        Implementation of lipid screening guidelines in children by primary pediatric providers.
        J Pediatr. 2014; 164: 572-576
        • McCrindle B.W.
        • Tyrrell P.N.
        • Kavey R.E.
        Will obesity increase the proportion of children and adolescents recommended for a statin?.
        Circulation. 2013; 128: 2162-2165
        • Bednarczyk D.
        • Boiselle C.
        Organic anion transporting polypeptide (OATP)-mediated transport of coproporphyrins I and III.
        Xenobiotica. 2016; 46: 457-466
        • Mori D.
        • Kimoto E.
        • Rago B.
        • et al.
        Dose-Dependent Inhibition of OATP1B by Rifampicin in Healthy Volunteers: Comprehensive Evaluation of Candidate Biomarkers and OATP1B Probe Drugs.
        Clin Pharmacol Ther. 2020; 107: 1004-1013
        • Zimmerman E.I.
        • Hu S.
        • Roberts J.L.
        • et al.
        Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide.
        Clin Cancer Res. 2013; 19: 1458-1466
        • Hsiang B.
        • Zhu Y.
        • Wang Z.
        • et al.
        A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters.
        J Biol Chem. 1999; 274: 37161-37168
        • Nakai D.
        • Nakagomi R.
        • Furuta Y.
        • et al.
        Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes.
        J Pharmacol Exp Ther. 2001; 297: 861-867
        • Ho R.H.
        • Tirona R.G.
        • Leake B.F.
        • et al.
        Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics.
        Gastroenterology. 2006; 130: 1793-1806
        • Bins S.
        • van Doorn L.
        • Phelps M.A.
        • et al.
        Influence of OATP1B1 Function on the Disposition of Sorafenib-beta-D-Glucuronide.
        Clin Transl Sci. 2017; 10: 271-279