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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Effect of Liver Disease on Hepatic Transporter Expression and Function
Nilay Thakkar1, Jason R Slizgi1, Kim L R Brouwer1
1Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
Journal of Pharmaceutical Sciences
|May 4, 2017
Summary
Liver disease impacts how the body processes drugs by altering hepatic transporter function. This review explores these changes to improve drug safety and efficacy in patients with liver conditions.
Area of Science:
- Pharmacology
- Hepatology
- Drug Metabolism
Background:
- Liver disease significantly affects xenobiotic and endogenous substance disposition.
- Regulatory agencies recommend evaluating drug effects in liver disease patients.
- While drug-metabolizing enzymes are well-studied, hepatic transporter alterations in liver disease are increasingly recognized.
Purpose of the Study:
- To review recent advancements in understanding hepatic transporter expression and function in liver disease.
- To highlight the implications of these changes on drug disposition, safety, and efficacy.
- To provide a foundation for future research and clinical practice.
Main Methods:
- Review of existing literature on hepatic transporter function in various liver diseases.
- Inclusion of data on drug-metabolizing enzymes and transporter proteins.
- Presentation of nonclinical data from animal models where clinical data is lacking.
Main Results:
- Liver disease alters both the expression and function of key hepatic transporters.
- Specific liver conditions like cholestasis, hepatitis C, and hepatocellular carcinoma show distinct transporter changes.
- Altered transporters can lead to significant changes in how drugs are absorbed, distributed, metabolized, and excreted.
Conclusions:
- Understanding hepatic transporter alterations is crucial for managing drug therapy in liver disease.
- Changes in transporter function necessitate careful dose adjustments for many medications.
- This review provides critical insights for drug development and patient care in hepatology.
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