Measuring altered disposition of xenobiotics in experimental models of liver disease

Rhiannon N. Hardwick, Nathan J Cherrington

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Understanding the metabolic pathway and excretion mechanisms governing the disposition of a compound is essential to the safe use of pharmaceutical agents. Because the liver is the primary organ responsible for the metabolism and elimination of xenobiotics, chronic liver disease can have a significant effect on the disposition of many xenobiotics due to changes in the expression or function of drug metabolizing enzymes and transporters. Liver disease can result in increased retention of a xenobiotic within the body, causing greater exposure of the individual to a potentially harmful compound, whichmay lead to toxicity. On the other hand, liver disease may also up-regulate the elimination processes of a xenobiotic, accelerating its removal from the body. With regard to a pharmaceutical agent, enhanced elimination may result in a decreased pharmacologic effect. Such alterations may necessitate dosage adjustments to achieve the desired therapeutic outcome.

Original languageEnglish (US)
Article number23.1
JournalCurrent protocols in toxicology / editorial board, Mahin D. Maines (editor-in-chief) ... [et al.]
Volume1
Issue numberSUPPL.52
DOIs
StatePublished - May 2012

Fingerprint

Xenobiotics
Liver
Liver Diseases
Theoretical Models
Pharmaceutical Preparations
Lead compounds
Metabolic Networks and Pathways
Metabolism
Toxicity
Chronic Disease
Up-Regulation
Enzymes
Therapeutics

Keywords

  • Drug disposition
  • Nonalcoholic fatty liver disease
  • Nonalcoholic steatohepatitis
  • Steatosis

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

@article{7ed8fdf0946a4ea1be85cfd1d5def0be,
title = "Measuring altered disposition of xenobiotics in experimental models of liver disease",
abstract = "Understanding the metabolic pathway and excretion mechanisms governing the disposition of a compound is essential to the safe use of pharmaceutical agents. Because the liver is the primary organ responsible for the metabolism and elimination of xenobiotics, chronic liver disease can have a significant effect on the disposition of many xenobiotics due to changes in the expression or function of drug metabolizing enzymes and transporters. Liver disease can result in increased retention of a xenobiotic within the body, causing greater exposure of the individual to a potentially harmful compound, whichmay lead to toxicity. On the other hand, liver disease may also up-regulate the elimination processes of a xenobiotic, accelerating its removal from the body. With regard to a pharmaceutical agent, enhanced elimination may result in a decreased pharmacologic effect. Such alterations may necessitate dosage adjustments to achieve the desired therapeutic outcome.",
keywords = "Drug disposition, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Steatosis",
author = "Hardwick, {Rhiannon N.} and Cherrington, {Nathan J}",
year = "2012",
month = "5",
doi = "10.1002/0471140856.tx2301s52",
language = "English (US)",
volume = "1",
journal = "Current protocols in toxicology / editorial board, Mahin D. Maines (editor-in-chief) ... [et al.]",
issn = "1934-9254",
publisher = "John Wiley and Sons Inc.",
number = "SUPPL.52",

}

TY - JOUR

T1 - Measuring altered disposition of xenobiotics in experimental models of liver disease

AU - Hardwick, Rhiannon N.

AU - Cherrington, Nathan J

PY - 2012/5

Y1 - 2012/5

N2 - Understanding the metabolic pathway and excretion mechanisms governing the disposition of a compound is essential to the safe use of pharmaceutical agents. Because the liver is the primary organ responsible for the metabolism and elimination of xenobiotics, chronic liver disease can have a significant effect on the disposition of many xenobiotics due to changes in the expression or function of drug metabolizing enzymes and transporters. Liver disease can result in increased retention of a xenobiotic within the body, causing greater exposure of the individual to a potentially harmful compound, whichmay lead to toxicity. On the other hand, liver disease may also up-regulate the elimination processes of a xenobiotic, accelerating its removal from the body. With regard to a pharmaceutical agent, enhanced elimination may result in a decreased pharmacologic effect. Such alterations may necessitate dosage adjustments to achieve the desired therapeutic outcome.

AB - Understanding the metabolic pathway and excretion mechanisms governing the disposition of a compound is essential to the safe use of pharmaceutical agents. Because the liver is the primary organ responsible for the metabolism and elimination of xenobiotics, chronic liver disease can have a significant effect on the disposition of many xenobiotics due to changes in the expression or function of drug metabolizing enzymes and transporters. Liver disease can result in increased retention of a xenobiotic within the body, causing greater exposure of the individual to a potentially harmful compound, whichmay lead to toxicity. On the other hand, liver disease may also up-regulate the elimination processes of a xenobiotic, accelerating its removal from the body. With regard to a pharmaceutical agent, enhanced elimination may result in a decreased pharmacologic effect. Such alterations may necessitate dosage adjustments to achieve the desired therapeutic outcome.

KW - Drug disposition

KW - Nonalcoholic fatty liver disease

KW - Nonalcoholic steatohepatitis

KW - Steatosis

UR - http://www.scopus.com/inward/record.url?scp=84865640622&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865640622&partnerID=8YFLogxK

U2 - 10.1002/0471140856.tx2301s52

DO - 10.1002/0471140856.tx2301s52

M3 - Article

C2 - 22549269

AN - SCOPUS:84865640622

VL - 1

JO - Current protocols in toxicology / editorial board, Mahin D. Maines (editor-in-chief) ... [et al.]

JF - Current protocols in toxicology / editorial board, Mahin D. Maines (editor-in-chief) ... [et al.]

SN - 1934-9254

IS - SUPPL.52

M1 - 23.1

ER -