Journal article
Breast cancer resistance protein (ABCG2) in clinical pharmacokinetics and drug interactions: practical recommendations for clinical victim and perpetrator drug-drug interaction study design
Drug metabolism and disposition, Vol.43(4), pp.490-509
04/2015
Handle:
https://hdl.handle.net/2376/110812
PMID: 25587128
Abstract
Breast cancer resistance protein (BCRP; ABCG2) limits intestinal absorption of low-permeability substrate drugs and mediates biliary excretion of drugs and metabolites. Based on clinical evidence of BCRP-mediated drug-drug interactions (DDIs) and the c.421C>A functional polymorphism affecting drug efficacy and safety, both the US Food and Drug Administration and European Medicines Agency recommend preclinical evaluation and, when appropriate, clinical assessment of BCRP-mediated DDIs. Although many BCRP substrates and inhibitors have been identified in vitro, clinical translation has been confounded by overlap with other transporters and metabolic enzymes. Regulatory recommendations for BCRP-mediated clinical DDI studies are challenging, as consensus is lacking on the choice of the most robust and specific human BCRP substrates and inhibitors and optimal study design. This review proposes a path forward based on a comprehensive analysis of available data. Oral sulfasalazine (1000 mg, immediate-release tablet) is the best available clinical substrate for intestinal BCRP, oral rosuvastatin (20 mg) for both intestinal and hepatic BCRP, and intravenous rosuvastatin (4 mg) for hepatic BCRP. Oral curcumin (2000 mg) and lapatinib (250 mg) are the best available clinical BCRP inhibitors. To interrogate the worst-case clinical BCRP DDI scenario, study subjects harboring the BCRP c.421C/C reference genotype are recommended. In addition, if sulfasalazine is selected as the substrate, subjects having the rapid acetylator phenotype are recommended. In the case of rosuvastatin, subjects with the organic anion-transporting polypeptide 1B1 c.521T/T genotype are recommended, together with monitoring of rosuvastatin's cholesterol-lowering effect at baseline and DDI phase. A proof-of-concept clinical study is being planned by a collaborative consortium to evaluate the proposed BCRP DDI study design.
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- Title
- Breast cancer resistance protein (ABCG2) in clinical pharmacokinetics and drug interactions: practical recommendations for clinical victim and perpetrator drug-drug interaction study design
- Creators
- Caroline A Lee - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Meeghan A O'Connor - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Tasha K Ritchie - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Aleksandra Galetin - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Jack A Cook - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Isabelle Ragueneau-Majlessi - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Harma Ellens - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Bo Feng - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Mitchell E Taub - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Mary F Paine - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Joseph W Polli - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Joseph A Ware - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.)Maciej J Zamek-Gliszczynski - Drug Metabolism and Pharmacokinetics, QPS LLC, Research Triangle Park, North Carolina (C.A.L.); Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (M.A.O., M.E.T.); Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom (A.G.); Pharmacokinetics and Drug Metabolism (B.F.) and Clinical Pharmacology, Global Innovative Pharma Business (J.A.C.), Pfizer Inc., Groton, Connecticut; School of Pharmacy, University of Washington, Seattle, Washington (I.R.-M., T.K.R.); Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina (M.J.Z.-G., J.W.P.) and King of Prussia, Pennsylvania (H.E.); College of Pharmacy, Washington State University, Spokane, Washington (M.F.P.); and Clinical Pharmacology, Genentech, South San Francisco, California (J.A.W.) maciej.x.zamek-gliszczynski@gsk.com
- Publication Details
- Drug metabolism and disposition, Vol.43(4), pp.490-509
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- United States
- Identifiers
- 99900547254601842
- Language
- English
- Resource Type
- Journal article