Clearance prediction of targeted covalent inhibitors by in vitro-in vivo extrapolation of hepatic and extrahepatic clearance mechanisms

Drug Metabolism and Disposition

Volumn 45, Issue 1, 2017, Pages 1-7

  Leung, Louis ^a   Yang, Xin ^a   Strelevitz, Timothy J ^a   Montgomery, Justin ^b   Brown, Matthew F ^b   Zientek, Michael A ^b   Banfield, Christopher ^b   Gilbert, Adam M ^d   Thorarensen, Atli ^c   Dowty, Martin E ^a  

^a PFIZER INC   (United States)

^b Pfizer Global Research and Development ^*  (United States)

^c Departments of Medicinal Chemistry   (United States)

^d Clinical Research Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANERTINIB; ETACRYNIC ACID; IBRUTINIB; DRUG; GLUTATHIONE; PROTEIN BINDING; PROTEIN KINASE INHIBITOR;

AEROBIC METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG MECHANISM; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIMIT OF QUANTITATION; LIVER CELL; MALE; MOUSE; NONHUMAN; PROCESS OPTIMIZATION; RAT; ALGORITHM; ANIMAL; BIOLOGICAL MODEL; BLOOD; C57BL MOUSE; LIVER MICROSOME; METABOLIC CLEARANCE RATE; METABOLISM; PLASMA; PRECLINICAL STUDY; PREDICTIVE VALUE; SPECIES DIFFERENCE; SPRAGUE DAWLEY RAT;

ALGORITHMS; ANIMALS; DRUG EVALUATION, PRECLINICAL; GLUTATHIONE; HEPATOCYTES; HUMANS; IN VITRO TECHNIQUES; MALE; METABOLIC CLEARANCE RATE; MICE, INBRED C57BL; MICROSOMES, LIVER; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS; PLASMA; PREDICTIVE VALUE OF TESTS; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; RATS; RATS, SPRAGUE-DAWLEY; SPECIES SPECIFICITY;

EID: 85009885070     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.116.072983     Document Type: Article

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