What is it about?
Accurate prediction of drug clearance (a metric that determine drug elimination rate in a patient's body) is necessary to individualize drug doses in patients in order to deliver safe and effective medication. Majority of drugs are eliminated by liver, and liver volume (LV) is a reasonable predictor of drug clearance. However, in obese individuals, a substantial part of liver is filled with liver fat (LF), which does not take part in drug elimination. Therefore, in obese individuals, lean liver volume (LLV) (where LLV = LV - LF) should be a better predictor of drug clearance than LV. In this work, we have shown the potential use of LLV in predicting drug clearance in obese individuals with the help of a model drug antipyrine.
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Why is it important?
Until now, liver fat was not accounted for while predicting drug clearance in the obese. Obese individuals accumulates substantial amount of liver fat (known as steatosis), which has been found to be as high as ~50% of liver volume. Therefore, prediction of drug clearance in the obese can be erroneous, if liver fat has not been accounted for. Here, we have demonstrated the potential use of lean liver volume (LLV), a novel descriptor of liver size that accounts for liver fat as well, in predicting drug clearance in the obese.
Perspectives
This article is important to understand the concept and potential utility of a novel liver size metric lean liver volume (LLV), that can be further explored in prediction of drug clearance in the obese. Use of LLV would be particularly helpful in physiology-based pharmacokinetic (PBPK) modeling, when applied to predict the time course of drugs in the obese population.
JAYDEEP SINHA
University of North Carolina at Chapel Hill Louis Round Wilson Special Collections Library
Read the Original
This page is a summary of: Evaluating Lean Liver Volume as a Potential Scaler for In Vitro-In Vivo Extrapolation of Drug Clearance in Obesity Using the Model Drug Antipyrine, Current Drug Metabolism, December 2020, Bentham Science Publishers,
DOI: 10.2174/1389200221666200515105800.
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