Drug disposition in obese humans. An update

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Obesity Research
• Clinical Pharmacology

Background:

• Obesity significantly alters body composition and physiology, potentially impacting drug disposition.
• Understanding how obesity influences drug absorption, distribution, metabolism, and excretion (ADME) is crucial for safe and effective pharmacotherapy.

Purpose of the Study:

• To review and synthesize current knowledge on drug disposition in obese individuals.
• To identify patterns and inconsistencies in how obesity affects various pharmacokinetic parameters.
• To highlight the need for further research into the mechanisms underlying altered drug disposition in obesity.

Main Methods:

• Literature review of studies investigating drug disposition in obese populations.
• Analysis of pharmacokinetic data for various drug classes in individuals with obesity.
• Examination of factors influencing drug distribution, protein binding, and clearance.

Main Results:

• Drug absorption is generally unchanged in obesity.
• Volume of distribution increases significantly for lipophilic drugs (e.g., benzodiazepines) and modestly for others (e.g., ibuprofen).
• Distribution is unchanged for some drugs (e.g., digoxin).
• Oxidative metabolism is minimally affected, while conjugation increases with bodyweight.
• Renal clearance shows variable changes depending on the drug.
• Protein binding to alpha 1-acid glycoprotein may increase but findings are inconsistent.

Conclusions:

• Obesity leads to variable changes in drug pharmacokinetics, particularly affecting volume of distribution and drug clearance.
• The mechanisms driving these pharmacokinetic alterations in obesity are complex and not fully understood.
• Further research, including the use of animal models, is needed to elucidate these mechanisms and optimize drug therapy for obese patients.