Elimination

Drugs are excreted or eliminated from the body as parent compounds or metabolites. The organs involved in excretion, with the exception of the lungs, eliminate water soluble compounds more readily than lipophilic substances. The lungs are important for the elimination of anaesthetic gases and vapors. The processes of biotransformation generally produce more polar compounds for excretion. The most important excretory organ is the kidney. Substances in the feces are mainly unabsorbed drugs administered orally or compounds excreted into the bile and not reabsorbed. Drugs may also be excreted in breast milk14 and even though the amounts are small, they represent an important pathway because the recipient of any drugs by this route is the nursing infant.

For a comprehensive discussion of renal excretion of drugs, the reader is referred to Weiner and Mudge.15 Excretion of drugs and their metabolites involves three processes, namely, glomerular filtration, passive tubular reabsorption, and active tubular secretion. The amount of a drug that enters the tubular lumen of the kidney is dependent on the glomerular filtration rate and the fraction of drug that is plasma protein bound. In the proximal renal tubular organic anions and cations are added to the filtrate by active transport processes. Glucuronide drug metabolites are secreted in this way by the carrier mediated system for naturally occurring organic acids. In the proximal and distal tubules of the kidney, the nonionized forms of weak acids and bases are passively reabsorbed. The necessary concentration gradient is created by the reabsorption of water with sodium. The passive reabsorption of ionized forms is pH dependent because the tubular cells are less permeable to these moieties. Therefore, in the treatment of drug poisoning, the excretion of some drugs can be increased by alkalinization or acidification of the urine.

Under normal physiological conditions, excretion of drugs in the sweat, saliva, and by the lacrimal glands is quantitatively insignificant. Elimination by these routes is dependent on pH and diffusion of the unionized lipid soluble form of the drug through the epithelial cells of the glands. Drugs excreted in saliva enter the mouth and may be reabsorbed and swallowed. Drugs have also been detected in hair and skin, and although quantitatively unimportant, these routes may be useful in drug detection and therefore have forensic significance.

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