ADMET 6

ADMET: Metabolism: Overview, Sites, and Influencing Factors

Overview of ADMET

  • ADMET refers to the four key components in drug pharmacokinetics and pharmacodynamics:

    • Absorption

    • Distribution

    • Metabolism

    • Excretion

  • It is crucial for understanding drug behavior in the body and ultimately affects therapeutic outcomes.

Additional Key Components in Detail

  • Absorption

    • Routes and sites of administration.

    • Mechanisms of absorption, including prodrugs and absorption-based drug-drug interactions (DDIs).

  • Distribution

    • Involves models of distribution and understanding volume of distribution.

    • Includes sequestration processes and blood-brain barrier (BBB) or CNS penetration, related to distribution-based DDIs.

  • Metabolism

    • The focus of this section:

    • Sites of metabolism and factors that influence them.

    • Types of chemical reactions involved in drug metabolism.

    • Metabolic pathways and enzymes.

    • Consideration of metabolism-based DDIs.

  • Elimination

    • Overview of routes of clearance and influencing factors.

Importance of Metabolism

  • Understanding metabolism is critical for several reasons:

    • Affects drug action and efficacy in the body.

    • Required to activate most prodrugs, converting them into their active forms.

    • Can generate active metabolites that enhance therapeutic effects.

    • Responsible for the formation of toxic metabolites that may lead to adverse effects.

    • Plays a vital role in drug-drug and drug-food interactions, impacting overall drug therapy effectiveness.

    • Subject to pharmacogenetic variation, which can alter metabolic responses among individuals.

Learning Objectives

  • Students should be able to:

    • List and explain how metabolism influences drug therapy.

    • Identify and describe various sites of drug metabolism.

    • Differentiate between the two major phases of drug metabolism.

    • Explain the effect of pharmacogenetic differences on drug metabolism.

    • Recognize factors influencing metabolism, specifically in aging populations or patients with special conditions.