Drug Elimination

Abstract

Most drugs, especially toxicants, are lipophilic in nature and once absorbed, would remain inside the body, distributing between tissues indefinitely unless they are converted to polar substances and excreted from the body. Drug elimination is the process that permanently removes drugs from the body. It may occur physically by excretion or chemically by metabolism, and is responsible for the termination of most drug actions. Drug metabolism is the single most important pharmacokinetic process that accounts for many of the inter-individual variations seen in therapeutic drug responses, and the liver is the main organ involved. Both internal (e.g., age, diseases or genetic factors) and external (e.g., diet or environment) factors may affect the rate or extent of drug metabolism. The metabolism of drugs usually results in water soluble metabolites which are readily excreted, and this generally occurs in the kidneys. The processes involved in the renal excretion of drugs are glomerular filtration, active tubular secretion and passive tubular reabsorption. While the former two processes facilitate drug excretion and are not affected by urine pH, the latter one decreases drug excretion and is pH-dependent. The two pharmacokinetic parameters that are related to drug elimination are drug clearance (CL) and plasma half-life (t _½ ). Drugs with high clearance (e.g., lidocaine, propranolol, morphine) display flow-dependent elimination, whereas drugs with low clearance (e.g., phenytoin, ethanol) exhibit capacity-limited elimination.