title: Contribution of metabolites to P450 inhibition-based drug-drug interactions: scholarship from the drug metabolism leadership group of the innovation and quality consortium metabolite group.
abstract: Recent European Medicines Agency (final) and US Food and Drug Administration (draft) drug interaction guidances proposed that human circulating metabolites should be investigated in vitro for their drug-drug interaction (DDI) potential if present at ≥ 25% of the parent area under the time-concentration curve (AUC) (US Food and Drug Administration) or ≥ 25% of the parent and ≥ 10% of the total drug-related AUC (European Medicines Agency). To examine the application of these regulatory recommendations, a group of scientists, representing 18 pharmaceutical companies of the Drug Metabolism Leadership Group of the Innovation and Quality Consortium, conducted a scholarship to assess the risk of contributions by metabolites to cytochrome P450 (P450) inhibition-based DDIs. The group assessed the risk of having a metabolite as the sole contributor to DDI based on literature data and analysis of the 137 most frequently prescribed drugs, defined structural alerts associated with P450 inhibition/inactivation by metabolites, and analyzed current approaches to trigger in vitro DDI studies for metabolites. The group concluded that the risk of P450 inhibition caused by a metabolite alone is low. Only metabolites from 5 of 137 drugs were likely the sole contributor to the in vivo P450 inhibition-based DDIs. Two recommendations were provided when assessing the need to conduct in vitro P450 inhibition studies for metabolites: 1) consider structural alerts that suggest P450 inhibition potential, and 2) use multiple approaches (e.g., a metabolite cut-off value of 100% of the parent AUC and the R(met) strategy) to predict P450 inhibition-based DDIs caused by metabolites in the clinic.
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.) hongbin.yu@boehringer-ingelheim.com.
authors: Hongbin
authors: H
authors: Yu
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Suresh K
authors: SK
authors: Balani
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Weichao
authors: W
authors: Chen
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Donghui
authors: D
authors: Cui
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Ling
authors: L
authors: He
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: W Griffith
authors: WG
authors: Humphreys
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Jialin
authors: J
authors: Mao
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: W George
authors: WG
authors: Lai
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Anthony J
authors: AJ
authors: Lee
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Heng-Keang
authors: HK
authors: Lim
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Christopher
authors: C
authors: MacLauchlin
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Chandra
authors: C
authors: Prakash
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Sekhar
authors: S
authors: Surapaneni
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Susanna
authors: S
authors: Tse
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Alana
authors: A
authors: Upthagrove
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Robert L
authors: RL
authors: Walsky
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Bo
authors: B
authors: Wen
authors: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.).
authors: Zhaopie
authors: Z
authors: Zeng
mesh_terms: D019540:Area Under Curve; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004345:Drug Industry / Q000331:legislation & jurisprudence; D004347:Drug Interactions; D005060:Europe; D005257:Fellowships and Scholarships; D033161:Government Regulation; D017408:Guidelines as Topic; D006801:Humans; D055553:Prescription Drugs / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D018570:Risk Assessment / Q000191:economics / Q000331:legislation & jurisprudence / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D055553:Prescription Drugs; D003577:Cytochrome P-450 Enzyme System