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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 4/2020

01-04-2020 | Original Research Article

Evaluating the Relationship Between Lean Liver Volume and Fat-Free Mass

Authors: Jaydeep Sinha, Stephen B. Duffull, Bruce Green, Hesham S. Al-Sallami

Published in: Clinical Pharmacokinetics | Issue 4/2020

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Abstract

Background

Fat-free mass has gained wide acceptance as a scaler of the maintenance dose rate in obese patients. The choice of fat-free mass as a size scaler for the maintenance dose rate is based on its relationship with drug clearance, on the basis that only lean tissue is sufficiently metabolically active to provide capacity for elimination. For xenobiotics, the majority of biotransformation occurs in the liver and hence fat-free mass is implied to scale linearly with the component of liver that is metabolically active. The liver, like the body, can be assumed to comprise two components, lean mass and fat mass. We expect the lean liver mass (or volume) to be the component that most closely relates to drug clearance.

Objective

The objective of this study was to investigate the relationship of lean liver volume and fat-free mass.

Methods

Total liver volume and liver fat volume were measured in 100 Indian adults by computed tomography. Lean liver volume was derived as the difference between the two measurements (as liver volume − liver fat volume). Covariate modelling to describe lean liver volume, using NONMEM version 7.3, involved testing the influence of body weight, sex, body surface area and fat-free mass with or without allometric scaling (by estimating the exponent) and the influence of clinical chemistry variables.

Results

The final model did not exclude a linear relationship between lean liver volume and fat-free mass, while allometric scaling by body weight0.75 was also supported by the data. While scaling by fat-free mass, the coefficient of proportionality (i.e. lean liver volume per kg fat-free mass) was higher in female (31.25 mL) than male (25.81 mL) subjects.

Conclusions

A model to predict lean liver volume from readily available patient data was developed and evaluated. Fat-free mass plus sex was found to be the best body descriptor to scale lean liver volume. The utility of this model in scaling drug clearance and dose requirements of hepatically cleared drugs needs further exploration.
Appendix
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Metadata
Title
Evaluating the Relationship Between Lean Liver Volume and Fat-Free Mass
Authors
Jaydeep Sinha
Stephen B. Duffull
Bruce Green
Hesham S. Al-Sallami
Publication date
01-04-2020
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 4/2020
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00824-7

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