Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability

John D Clarke; Nathan J Cherrington

doi:10.1016/j.pharmthera.2015.03.005

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Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability

Journal article

Open access

Peer reviewed

Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability

John D Clarke and Nathan J Cherrington

Pharmacology & therapeutics (Oxford), Vol.151, pp.99-106

07/2015

DOI: https://doi.org/10.1016/j.pharmthera.2015.03.005

Handle:

https://hdl.handle.net/2376/101427

PMCID: PMC4457694

PMID: 25805597

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https://doi.org/10.1016/j.pharmthera.2015.03.005View

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Abstract

Pharmacogenetics

Non-alcoholic Fatty Liver Disease - genetics

Biotransformation

Humans

Liver - metabolism

Membrane Transport Proteins - metabolism

Non-alcoholic Fatty Liver Disease - metabolism

Gene-Environment Interaction

Non-alcoholic Fatty Liver Disease - drug therapy

Precision Medicine

There are numerous factors in individual variability that make the development and implementation of precision medicine a challenge in the clinic. One of the main goals of precision medicine is to identify the correct dose for each individual in order to maximize therapeutic effect and minimize the occurrence of adverse drug reactions. Many promising advances have been made in identifying and understanding how factors such as genetic polymorphisms can influence drug pharmacokinetics (PK) and contribute to variable drug response (VDR), but it is clear that there remain many unidentified variables. Underlying liver diseases such as nonalcoholic steatohepatitis (NASH) alter absorption, distribution, metabolism, and excretion (ADME) processes and must be considered in the implementation of precision medicine. There is still a profound need for clinical investigation into how NASH-associated changes in ADME mediators, such as metabolism enzymes and transporters, affect the pharmacokinetics of individual drugs known to rely on these pathways for elimination. This review summarizes the key PK factors in individual variability and VDR and highlights NASH as an essential underlying factor that must be considered as the development of precision medicine advances. A multifactorial approach to precision medicine that considers the combination of two or more risk factors (e.g. genetics and NASH) will be required in our effort to provide a new era of benefit for patients.

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Title: Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability
Creators: John D Clarke - Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, United States
Nathan J Cherrington - Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, United States. Electronic address: cherrington@pharmacy.arizona.edu
Publication Details: Pharmacology & therapeutics (Oxford), Vol.151, pp.99-106
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: England
Grant note: HD062489 / NICHD NIH HHS R01 AI083927 / NIAID NIH HHS T32 ES007091 / NIEHS NIH HHS DK068039 / NIDDK NIH HHS ES007091 / NIEHS NIH HHS R01 HD062489 / NICHD NIH HHS P30 ES006694 / NIEHS NIH HHS
Identifiers: 99900546573901842
Language: English
Resource Type: Journal article