The kidneys are the major organs for excretion of water-soluble substances. The biliary system contributes to the extent of excretion, are not reabsorbed in the drug in the gastrointestinal tract. Except for the exhalation of volatile anesthetics, the contribution of intestinal, saliva, sweat, breast milk and lungs for excretion is generally low. The excretion via breast milk can on a breastfed child influence (see table: Some medications that are contraindicated for nursing mothers).
(See also Overview pharmacokinetics.) The kidneys are the major organs for excretion of water-soluble substances. The biliary system contributes to the extent of excretion, are not reabsorbed in the drug in the gastrointestinal tract. Except for the exhalation of volatile anesthetics, the contribution of intestinal, saliva, sweat, breast milk and lungs for excretion is generally low. The excretion via breast milk can on a breastfed child influence (see table: Some medications that are contraindicated for nursing mothers). The hepatic metabolism often increases the polarity and Wasserlösichkeit of drugs. The resulting metabolites are then easily excreted. Urinary excretion Renal filtration is responsible for the bulk of the drug excretion. Approximately one fifth of the plasma that reaches the glomerulus is filtered through pores in the Glomerulusendothel. Almost all of the water and most electrolytes are passively and actively reabsorbed by the renal tubule back into the circulation. However, polar compounds, and therefore most drug metabolites, not diffuse back into the cycle; they are excreted unless a specific transport mechanism for their reabsorption exists (z. B. as for glucose, ascorbic acid and B vitamins). When aging renal excretion decreases see table: effects of aging on metabolism * and elimination of some drugs). Typically, the clearance of 80 years is only half as high as it was at the age of 30 years. determine the principles of the transmembrane passage, such as the kidney handles the drug. The glomerular filtrate contains only unbound drug. Drugs that are bound to plasma proteins remain in circulation. Ionized forms of drugs and their metabolites tend to be easily reabsorbed from the tubular fluid. The pH of the urine, which varies of 4.5 to 8.0 can significantly affect the resorption and excretion of drugs, since it determines the ionization rate of a weak acid or base (passive diffusion). Acidification of urine increases the reabsorption and reduces the excretion of weak acids and in turn the reabsorption of weak bases. Alkalization of urine has the opposite effect. For example, the urine is alkalized in order to enhance the precipitation of salicylic acid. In some cases of overdose these principles are exploited in order to increase the excretion of weak bases or acids. The extent to alter the rate of elimination of drugs in which changes of pH depends on the renal contribution to the total elimination of the polarity of the non-ionized form and the degree of ionization of the molecule. Active tubular secretion in the proximal tubule is important for the elimination of many drugs. This energy-dependent process can be blocked by metabolic inhibitors. Each substance has its characteristic transport maximum. When the drug concentration is high, the secretory transport can reach an upper limit (transport maximum). Anions and cations are subject to different transport mechanisms. Normally, the secretory system for anions metabolites are conjugated with glycine, sulfate or glucuronic eliminated. Anions compete with one another for secretion. This competition can be used therapeutically. For example, probenecid blocks the rapid tubular secretion of penicillin, resulting in higher plasma concentrations of penicillin over a longer period. In the cation transport system cations or organic bases (z. B. pramipexole, dofetilide [not available in Germany]) are secreted in the renal tubule. This process can by cimetidine, trimethoprim, prochlorperazine (not available in Germany), megestrol or ketoconazole inhibited. Biliary excretion Some drugs and their metabolites are excreted to a large extent in the bile. As they are transported through the biliary epithelium against the concentration gradient, this is an active secretory transport is necessary. When the plasma drug concentrations are high, the secretory transport can reach an upper limit (transport maximum). Substances with similar physicochemical properties may compete for excretion. Smaller molecules are excreted generally in only negligible amounts. Drugs with a molecular weight of about 300 g / mol and with both polar and lipophilic groups are eliminated with higher probability in the bile. Conjugation, particularly with glucuronic acid facilitates biliary excretion. Enterohepatic cycle a secreted into bile medicines in the intestine is reabsorbed into the circulation. The biliary excretion substances eliminated from the body only to the extent in which the enterohepatic cycle is incomplete – if a portion of discharged drug is not reabsorbed in the gut.