# Structural Biochemistry/ADME

ADME is the acronym commonly used in pharmacology and pharmacokinetics used to reference the four basic stages of a drug/medicine's life inside the human's body: Absorption, Distribution, Metabolism, and Excretion.

## Absorption

Absorption is the transfer of a drug into the blood after it is released from its dosage formulation. The body can absorb drugs in many ways, such as oral (swallowing an tylenol tablet), intramuscular (getting a flu shot in an arm muscle), subcutaneous (injecting insulin just under the skin), intravenous (receiving chemotherapy through a vein), or transdermal (wearing a skin patch). The most common way is through oral administration. Once the drug has been absorbed it gets shuttled by a special blood vessel where it enters from the digestive tract to the liver, and this is where a large amount of the drug may be destroyed by metabolic enzymes (often called "first-pass effect." One of the most important factors affecting oral drug absorption is the gastric emptying time. The gastric emptying time is the time a drug will stay in the stomach before it is emptied into the small intestine. This time affects a drug's action because most drugs are absorbed in the intestine. Stomach acid can degrade many drugs before they reach the absorption stage. Once a drug leaves the stomach without being destroyed, its rate of movement through the intestines affects its current absorption. If the drug moves through the intestines slowly, more of the drug will be absorbed since it is in contact with the intestinal membrane for a long time. On the other hand, fast movement through the intestines might cause a drug to not be fully absorbed. In addition, bile salts and enzymes from the intestinal tract also affect the absorption of a drug. Bile salts improve the absorption of some hydrophobic drugs. However, enzymes decrease the absorption of drugs by destroying the drugs as they pass through.

## Distribution

Distribution is the movement of a drug inside the body once the drug has reached the blood. Blood carries the drug throughout the body and also to its sites of action. First, distribution is affected by the blood flow rates to certain organs. When an organ has a high blood flow rate such as in the heart, liver, and kidneys, the drug is distributed quickly. However, organs with slow blood flow rates like the muscle, fat, and skin, cause distribution to be much slower. Moreover, the permeability of tissue membranes to a drug is also extremely important. Small drug molecules and hydrophobic drugs will diffuse through tissue membranes easily. Also, there are some tissue membranes that have specialized transport mechanisms that assist penetration. However, there are some tissue membranes that are highly selective in allowing drugs to penetrate through. For example, the blood-brain barrier limits drug access to the brain. Lastly, protein binding can affect distribution as well. Most drugs bind to proteins in the blood plasma, forming what is called a complex. Because these complexes are large, it prevents the drug from entering its sites. So, only free or unbound drugs can move through the tissue membranes. Furthermore, some drugs with a stronger binding capacity can displace a weaker bound drug from a protein, making the weakly bound drug not bound anymore.

## Metabolism

Drug metabolism refers to the body's way of processing drugs. This drug that is being transformed inside the body is called a metabolite. Most metabolites are inactive molecules that are excreted but some are active and produce effects in a human until they are further metabolized or excreted. The liver is the primary site of drug metabolism. The enzymes found inside the liver interact with drugs and change them into metabolites. CYP3A4 is a drug-metabolizing enzyme in the intestines that increases or alters blood levels of certain medications in people. CYP450 is a cytochrome enzyme that processes essential molecules such as hormones and vitamins a well as metabolize hundreds of prescribed medicines and natural substances. Some drugs allow the liver to increase its enzyme activity, allowing the drug to result in greater metabolism. So, some doses of drugs must be larger to produce the same therapeutic effects. However, some drugs decrease enzyme activity. In this situation, smaller doses of the drug are needed to avoid toxicity. Also, the liver may secrete drugs into the bile that is stored in the gallbladder. Any drugs or metabolites in the bile may be reabsorbed or eliminated within the feces. If the drugs are reabsorbed back into the blood, it is called enterohepatic cycling.

## Excretion

Most drugs and their metabolites are excreted by the kidneys and come out of the body through urine. Some drugs are not easily absorbed from the gastrointestinal tract and so will be excreted in the feces rather than the urine. Excretion can also happen through the bile and some drugs are removed through the lungs in the expired breath. But, most drugs are excreted through the kidneys, which filters the blood and removes waste materials from the blood. Some of the plasma water is filtered from the blood into the nephron tubule in a process called glomerular filtration. This filtered water may have waster drugs from other parts of the body. As the water continues to move across the body, other waste drugs can be secreted into the fluid. While this is occurring, some drugs can be reabsorbed back into the blood through urinary reabsorption. After all of this happens, the final fluids are excreted from the body as urine. The rate of urinary excretion is much faster than that of fecal excretion. Drugs excreted through the urine take a couple of hours while drugs excreted through the feces take a couple of days.

## Reference

* The Pharmacy Technician. New York: Morton Publishing Company, 2007.
* Davis, Alison. Medicines by Design. [Bethesda, MD]: U.S. Dept. of Health and Human Services, National Institutes of Health, National Institute of General Medical Sciences, 2006. Print.