title: Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions-an Industry Perspective.
abstract: Under the guidance of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), scientists from 20 pharmaceutical companies formed a Victim Drug-Drug Interactions Working Group. This working group has conducted a review of the literature and the practices of each company on the approaches to clearance pathway identification (fCL), estimation of fractional contribution of metabolizing enzyme toward metabolism (fm), along with modeling and simulation-aided strategy in predicting the victim drug-drug interaction (DDI) liability due to modulation of drug metabolizing enzymes. Presented in this perspective are the recommendations from this working group on: 1) strategic and experimental approaches to identify fCL and fm, 2) whether those assessments may be quantitative for certain enzymes (e.g., cytochrome P450, P450, and limited uridine diphosphoglucuronosyltransferase, UGT enzymes) or qualitative (for most of other drug metabolism enzymes), and the impact due to the lack of quantitative information on the latter. Multiple decision trees are presented with stepwise approaches to identify specific enzymes that are involved in the metabolism of a given drug and to aid the prediction and risk assessment of drug as a victim in DDI. Modeling and simulation approaches are also discussed to better predict DDI risk in humans. Variability and parameter sensitivity analysis were emphasized when applying modeling and simulation to capture the differences within the population used and to characterize the parameters that have the most influence on the prediction outcome.
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.) tonika.bohnert@biogen.com.
authors.forename: Tonika
authors.initials: T
authors.lastname: Bohnert
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Aarti
authors.initials: A
authors.lastname: Patel
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Ian
authors.initials: I
authors.lastname: Templeton
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Chuang
authors.initials: C
authors.lastname: Lu
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: George
authors.initials: G
authors.lastname: Lai
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Louis
authors.initials: L
authors.lastname: Leung
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Susanna
authors.initials: S
authors.lastname: Tse
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Einolf
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Michael
authors.initials: M
authors.lastname: Sinz
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Ralph
authors.initials: R
authors.lastname: Stearns
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Robert
authors.initials: R
authors.lastname: Walsky
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Wanping
authors.initials: W
authors.lastname: Geng
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Sirimas
authors.initials: S
authors.lastname: Sudsakorn
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: David
authors.initials: D
authors.lastname: Moore
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Jan
authors.initials: J
authors.lastname: Wahlstrom
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Jim
authors.initials: J
authors.lastname: Keirns
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Rangaraj
authors.initials: R
authors.lastname: Narayanan
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Dieter
authors.initials: D
authors.lastname: Lang
authors.affiliation: Biogen, Cambridge, Massachusetts (T.B.); GlaxoSmithKline R&D, Hertfordshire, United Kingdom (A.P.); Janssen R&D, Spring House, Pennsylvania (I.T.); Genentech, South San Francisco, California (Y.C.); Takeda, Cambridge, Massachusetts (C.L.); Eisai Inc., Andover, Massachusetts (G.L.); Pfizer Inc., Groton, Connecticut (L.L., S.T.); Novartis, East Hanover, New Jersey (H.J.E.); Merck & Co., Inc., Kenilworth, New Jersey (Y.-H.W.); Bristol Myers Squibb, Wallingford, Connecticut (M.S.); Vertex Pharmaceuticals Inc., Boston, Massachusetts (R.S.); EMD Serono R&D Institute, Inc., Billerica, Massachusetts (R.W., W.G.); Sanofi, Waltham, Massachusetts (S.S.); Roche Innovation Center, New York, New York (D.M.); Daiichi Sankyo, Edison, New Jersey (L.H.); Amgen Inc., Thousand Oaks, California (J.W.); Astellas, Northbrook, Illinois (J.K.); Celgene Corporation, Summit, New Jersey (R.N.); Bayer Pharma AG, Wuppertal, Germany (D.L.); and Incyte Corporation, Wilmington, Delaware (X.Y.).
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001711:Biotransformation; D003198:Computer Simulation; D003663:Decision Trees; D055808:Drug Discovery / Q000379:methods / Q000592:standards*; D004345:Drug Industry / Q000592:standards*; D004347:Drug Interactions; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D018570:Risk Assessment; D013045:Species Specificity; D013379:Substrate Specificity
chemical_list: D004798:Enzymes; D004364:Pharmaceutical Preparations