From the Guidelines
The main processes of pharmacokinetics are absorption, distribution, metabolism, and excretion (ADME), which collectively determine a drug's concentration at its target site, its duration of action, and ultimately its therapeutic effect.
Overview of ADME
The process of absorption is the initial step where a drug enters the bloodstream after administration, which can occur through various routes such as oral, intravenous, or transdermal 1.
- Distribution refers to how the drug moves from the bloodstream to tissues and organs throughout the body, influenced by factors like blood flow, protein binding, and lipid solubility, with some drugs having high distribution volumes and fast distribution to the central nervous system 1.
- Metabolism primarily occurs in the liver where enzymes, including cytochrome P-450 and UDP-glucuronosyltransferases, transform drugs into metabolites, either activating prodrugs or preparing substances for elimination, with genetic polymorphisms affecting the metabolism of some drugs 1.
- Excretion is the removal of drugs and their metabolites from the body, mainly through the kidneys into urine, but also via bile, feces, lungs, sweat, or breast milk, with some drugs having low renal excretion and being mainly eliminated by hepatic metabolism 1.
Clinical Implications
Understanding these pharmacokinetic principles is crucial for clinicians to optimize dosing regimens, predict drug interactions, and adjust treatments for patients with impaired organ function, as highlighted in the management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease 1.
- The distribution of drugs, influenced by protein binding and lipophilicity, can affect their pharmacological effects, with most statins being highly protein bound and lipophilic, except for pravastatin and rosuvastatin 1.
- The interplay between these ADME processes and individual patient factors, such as genetic polymorphisms and organ function, necessitates a personalized approach to drug therapy to maximize efficacy and minimize adverse effects.
From the Research
Pharmacokinetics Processes
The main processes of pharmacokinetics are absorption, distribution, metabolism, and excretion (ADME) [ 2, 3, 4, 5, 6 ].
- Absorption: The process by which a drug is taken into the body and made available to the target site [ 3, 4, 5, 6 ].
- Distribution: The process by which a drug is transported to its target site and other parts of the body [ 3, 4, 5, 6 ].
- Metabolism: The process by which a drug is broken down into its metabolites [ 2, 3, 4, 5, 6 ].
- Excretion: The process by which a drug and its metabolites are eliminated from the body [ 2, 3, 4, 5, 6 ].
Importance of ADME
Understanding ADME processes is essential for drug development and precision medication [ 2 ]. ADME studies provide the only basis for critical judgments from situations where the behavior of the drug is understood to those where it is unknown [ 3 ].
Factors Affecting ADME
The chemical structures, dosage forms, and sites and routes of administration are the principal determinants of ADME profiles and consequent impacts on their efficacy and adverse drug reactions (ADRs) [ 6 ].
Unique ADME Characteristics
Newly developed large molecule biologic antisense oligonucleotide (ASO) drugs have completely unique ADME that is not fully defined [ 6 ]. Membrane permeabilization through endocytosis and nucleolytic degradation by endonucleases and exonucleases are major ADME features of the ASO drugs that differ from small-molecule drugs [ 6 ].