The ADMEs of Pharmacokinetics

Our bodies are like a manufacturing plant – constantly taking raw materials (food, medicine, etc.), transforming them into new things (nutrients, active APIs, etc.), using them, and then eventually removing the waste — but how does that work? And, more specifically, how does that work for medicines? Read on to learn more about the ADMEs of pharmacokinetics!

Pharmacokinetics is the way to describe how the body affects a substance after its administration. These substances can range from pharmaceuticals to food additives and even cosmetics.

There are 4 main phases in the pharmacokinetic process, found in the acronym ADME:
Absorption – Distribution – Metabolism – Excretion

The first phase, absorption, kicks off the journey of a drug entering the body and having its therapeutic effect. This is where a drug’s route of administration plays a big role in how effectively it’s absorbed by the body. Common routes of administration are:

Rate of absorption determines how quickly the drug enters the system and relates to its bioavailability). One of the most important aspects impacting this rate is dissolution. Dissolution is mostly relevant for oral administration and is impacted by the form factor of the drug.

Once dissolved, for oral drugs, the small intestine is the primary location for absorption. However, depending on the drug, many other parts of the body can absorb a drug, like the skin and intercellular fluids and tissues!

The second phase, distribution, describes how the absorbed drug reaches its intended target. The body is an incredibly complex network of organs, veins/arteries, nerves, and tissues – how does a drug make it to its target? By leveraging the super-highway that is our bloodstream!

From there, drugs can travel into or out of the bloodstream to spaces and bodily fluids (perfusion) – ultimately reaching the intended target. What affects this travel though?

Physical volume of the person: more volume = more space to travel through
Removal rate: how much of a drug is removed prior to reaching its target
Plasma protein binding: drugs can bind to proteins in blood, preventing them from being transferred elsewhere

Now that the drug has been absorbed and distributed throughout the body, what happens next? The final two phases of ADME take over. Read on to learn how the drugs are eventually used up and leave the body!

The third phase, metabolism, pertains to how the drugs are broken down in our body. You’re likely used to hearing about metabolism as it relates to eating food and how quickly your body breaks it down into energy and waste. It’s the same for drug metabolism!

For small-molecule drug metabolism, the primary mechanism is an enzymatic process, largely leveraging CYP450 enzymes in the liver.

These enzymes specialize in oxidation-reduction reactions that break down a drug into inert components. From there, the components can be excreted.

Metabolism for a biologic drug is a bit different as it is a protein and it’s broken down via intracellular processes that result in small peptide fragments or amino acids, that are then ready for excretion.

In general, increasing the rate of metabolism will decrease the bioavailability of a drug. Metabolism can be affected by a variety of factors, including age, genetics, nutrition, and even other drugs that could inhibit enzymes – as found with the CYP34A enzyme and inhibitors.

Sometimes, metabolism isn’t just for inactivating drugs but can be used to activate them! These drugs are called prodrugs.

The final phase, excretion, is the process in which the metabolized components of the drug are removed from the body. This phase leverages the body’s excretory system, which consists of the kidneys and urinary system.

The kidneys are a pair of bean-shaped organisms that filter all of the blood flowing through the body. Blood traveling through the kidney will contain the unwanted metabolized components and these get pulled out into the rest of the urinary system to then be excreted in urine. This is the most common way for drugs to be excreted from the body.

Pharmacokinetics are a central part to development of a drug. They determine how effective a drug can be along with what considerations need to be made for dosages. The bioavailability of a drug is studied with in vitro and in vivo studies, prior to moving into clinical trials.

Fun Fact: In parallel to understanding how long a drug stays in the body, it’s equally important to understand what a healthy amount is!