Drugs are excreted (cleared) from the body either unchanged or as metabolites. The kidney is the most important organ responsible for clearance. Renal clearance may involve three processes: glomerular filtration which depends on fractional plasma protein binding and filtration rate; active tubular excretion, a non-selective carrier system for organic ions; and passive tubular reabsorption of unionized drugs.
Some drugs are cleared via the bile into the intestinal tract. These agents may subsequently be reabsorbed from the gut (enterohepatic recirculation), which contributes to higher bioavailability and prolonged drug action. Pulmonary excretion is important for the clearance of anesthetic gases and vapors. Drugs excreted in milk are potential sources of unwanted adverse effects in nursing infants. Other routes, such as saliva, sweat, and tears are quantitatively unimportant.
Drug clearance may be by first-order or zero-order kinetics. Most drugs are excreted by first-order kinetics, implying that a constant fraction of the drug is eliminated per unit time from the body. The clearance of some drugs (e.g., alcohol) follows zero-order kinetics, implying that a constant amount of the drug is eliminated per unit time. Zero-order kinetics tend to predominate in overdose as a result of saturation of metabolic and/or elimination pathways.
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