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

Area of Science:

• Pharmacokinetics
• Medical Imaging
• Human Physiology

Background:

• Fat-free mass (FFM) is widely used to scale drug maintenance doses in obese patients, assuming lean tissue drives drug clearance.
• This assumption implies FFM scales with metabolically active liver components responsible for drug biotransformation.
• The liver, like the body, comprises lean and fat mass; lean liver mass is hypothesized to correlate with drug clearance.

Purpose of the Study:

• To investigate the relationship between lean liver volume and fat-free mass.
• To develop a predictive model for lean liver volume using accessible patient data.

Main Methods:

• Computed tomography (CT) was used to measure total liver and liver fat volume in 100 Indian adults.
• Lean liver volume was calculated as total liver volume minus liver fat volume.
• Covariate modeling (NONMEM) assessed the influence of body weight, sex, body surface area, and FFM on lean liver volume.

Main Results:

• A linear relationship between lean liver volume and FFM was supported.
• Allometric scaling of lean liver volume by body weight to the power of 0.75 was also supported.
• The coefficient of proportionality for lean liver volume per kg FFM was higher in females (31.25 mL) than males (25.81 mL).

Conclusions:

• Fat-free mass and sex were identified as the best predictors for scaling lean liver volume.
• A model was developed to predict lean liver volume from readily available patient data.
• Further research is needed to explore the model's utility in scaling drug clearance for hepatically cleared drugs.