excretion
Definition
Excretion is the pharmacokinetic process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (renal excretion) and liver (biliary excretion), but also via lungs, sweat, and other routes. This process is critical for determining drug half-life, dosing intervals, and potential for accumulation. Renal excretion involves glomerular filtration, active tubular secretion, and passive tubular reabsorption, influenced by factors like molecular weight, protein binding, pH, and transporter activity. Impaired excretion due to kidney or liver disease can lead to drug toxicity, necessitating dose adjustments. Understanding excretion mechanisms is essential for predicting drug-drug interactions, particularly when multiple drugs compete for the same elimination pathways or when one drug inhibits excretory transporters.
Visualize excretion in Nodes Bio
Researchers can map excretion pathways as networks connecting drugs to renal and hepatic transporters (OAT, OCT, P-glycoprotein), metabolizing enzymes, and elimination routes. Network analysis reveals how genetic variants in transporter genes affect drug clearance, identifies potential drug-drug interactions through shared excretion pathways, and visualizes the cascade from drug administration through metabolic transformation to final elimination, enabling prediction of pharmacokinetic profiles.
Visualization Ideas:
- Drug-transporter interaction networks showing renal and hepatic elimination pathways
- Multi-drug competition networks for shared excretory transporters like OAT and OCT families
- Pharmacokinetic cascade networks linking absorption, distribution, metabolism, and excretion (ADME) processes
Example Use Case
A pharmaceutical team developing a novel kinase inhibitor discovers unexpected drug accumulation in Phase I trials. Using network analysis, they map the compound's excretion pathway, revealing that it's a substrate for OAT3 renal transporter, which is inhibited by a commonly co-prescribed proton pump inhibitor. The visualization shows competing substrates and identifies that 40% of target patients take OAT3 inhibitors, explaining the accumulation. This insight leads to revised dosing guidelines and contraindication warnings, preventing potential nephrotoxicity in clinical practice.