Human absorption, distribution, metabolism, and excretion studies: Conventional or microtracer?

Area of Science:

• Clinical Pharmacology
• Drug Development
• Pharmacokinetics

Background:

• Human absorption, distribution, metabolism, and excretion (hADME) studies are crucial for understanding small-molecule drug behavior.
• These studies inform safety, drug-drug interaction, and organ impairment assessments.
• Two primary hADME study types exist: conventional and microtracer.

Purpose of the Study:

• To comprehensively compare conventional and microtracer hADME study types.
• To review literature on the prevalence and characteristics of each study type.
• To provide recommendations for selecting the appropriate hADME study for investigational drugs.

Main Methods:

• Literature review of publications in 3 peer-reviewed journals (2010-2024) comparing conventional and microtracer hADME studies.
• Analysis of advantages and disadvantages of each study type.
• Discussion of specific scenarios favoring microtracer hADME studies.

Main Results:

• Conventional hADME studies were found to be approximately 7 times more prevalent than microtracer studies for small molecule and peptide drugs.
• Conventional studies offer ease, low cost, and flexibility in radiometric analysis.
• Microtracer studies offer advantages such as exemption from prerequisite studies and use of non-GMP 14C-labeled materials.

Conclusions:

• Both conventional and microtracer hADME studies have distinct advantages and disadvantages.
• Microtracer hADME studies may be preferable in certain clinical development scenarios.
• A decision tree is recommended for selecting the most appropriate hADME study type based on investigational drug characteristics.