Introduction
Elimination is a pharmacokinetic process that describes the irreversible removal of active pharmaceutical ingredients from the body. It is composed of biotransformation (metabolism) and excretion (elimination). The most important organs for excretion are the kidney and the liver. However, drugs can also be excreted through the respiratory tract, hair, saliva, milk, tears, and sweat. However, these routes are of lesser importance. For example, anesthetics and other volatile substances such as alcohol are eliminated through exhaled air.
Renal excretion (kidney).
The kidneys filter the blood and low-molecular-weight substances contained in it, such as pharmaceutical agents. In addition, these can also be actively secreted into the primary urine, i.e., with the expenditure of energy. Macromolecules such as the biologics (e.g. antibodies, proteins) do not enter the filtrate, which is one reason for their long half-life. 99% of the filtrate is reabsorbed back into the blood, so only a small portion is actually excreted as urine via the ureter, bladder and urethra. Thus, three processes are critical to the kidney: glomerular filtration, tubular secretion, and tubular reabsorption.
Hepatobiliary excretion (liver, bile).
Active substances can reach the liver with both venous and arterial blood. There, it mixes in the hepatic lobule area. The venous blood comes from the digestive tract, from which the active pharmaceutical ingredients were absorbed. The mixed venous-arterial blood is in contact with the liver cells, the hepatocytes, in the so-called liver sinusoids. Here, a lively active and passive exchange of substances takes place. The hepatocytes take up active substances, metabolize them and release them into the bile canaliculi. The bile flows through the bile ducts to the gallbladder and is finally released into the small intestine. From the intestine, the active ingredients can be reabsorbed. This is referred to as the enterohepatic circulation. Alternatively, they may be excreted in the stool.
Relevance to drug therapy
Excretion is a fundamental pharmacokinetic process. If it did not exist, active ingredients would remain in the body indefinitely, exerting their effects and adverse effects permanently after a dose. Important kinetic parameters such as half-life and clearance reflect elimination. They also help determine the dosing interval, i.e., the required intervals between the administration of doses. Molecular structures that are suitable as drug targets for drug therapy are found at the elimination organs. For example, the transporter SGLT2 is responsible for the reabsorption of glucose. If it is blocked, more glucose is excreted. Consequently, SGLT2 inhibitors are administered for the treatment of diabetes. An analogous example is the URAT1 inhibitors, which suppress the reabsorption of uric acid and are used to treat gout. : When the function of the eliminating organs is impaired, the risk of adverse and toxic effects increases. In the case of accumulation, there is an imbalance between intake and excretion. The plasma concentration of the active substance increases. Therefore, a dose reduction may be necessary. For example, patients receive only half a tablet instead of a whole tablet. The specific instructions can be found in the technical information. Drug-drug interactions result from inhibition or induction of transport systems involved in elimination.
