Drug administration and dosing regimens

Every medication can be administered through various means, known as routes of administration; and various schedules, meaning at a particular frequency and amount, or dose, which is known as the dosing regimen.

Alright, so routes of administration are broken down into three main categories: enteral, parenteral, and topical. In enteral administration, which is the most common form, the medication is administered through the gastrointestinal tract. This could mean that it’s swallowed by the mouth, also known as peroral administration; placed under the tongue, also known as sublingual administration; between the gums and the inner lining of the cheek, also known as buccal administration; or finally, into the rectum, also known as rectal administration.

On the other hand, parenteral administration includes any route that bypasses the gastrointestinal tract, to pump the medication directly into the circulation, such as through an injection into a vein, intravenously, or IV for short; under the skin, subcutaneously, or SC for short; or into muscle, intramuscularly, or IM for short. Finally, there’s topical administration, where the medication is applied directly upon a particular area of the skin or mucous membrane to achieve a local or systemic effect. An example of this is an antifungal cream used to treat athlete's foot locally or a clonidine patch to treat hypertension systemically.

Now, choosing the route of administration depends on many factors. First of all, these include the chemical properties of the medication itself, such as its stability, and its ability to cross certain barriers of absorption.

For example, a perorally administered medication needs to be able to resist tough, acidic conditions within the stomach, and then readily pass through the walls of the intestines into the blood. In addition to this, blood coming from the gastrointestinal tract is first directed to the liver. And that’s where many medications get broken down or metabolized before gaining their entry ticket to the systemic circulation. This means the medications are metabolized before they even get a chance to reach their target tissues. This is known as first-pass metabolism or the first-pass effect.

So, medications that get extensively metabolized into inactive forms through that first-pass shouldn’t be administered perorally as it would decrease their efficacy. In contrast, IV administration allows medications that are less stable, or less capable of being absorbed through the gastrointestinal tract, to be directly administered into the bloodstream, which is also beneficial for medications that have a major first-pass effect.

A practical measure of absorption is bioavailability. Bioavailability refers to the portion of a medication that reaches the systemic circulation when administered by non-intravenous routes. For example, if someone takes 100 mg of aspirin orally, and only 60 mg are absorbed into the circulation, the bioavailability is 0.6 or 60%. In contrast, the bioavailability of an intravenously administered medication is always 1 or 100%.

Another factor that should be taken into account for deciding the route of administration is the urgency of the situation. So for example, peroral medications take time to get absorbed in the GI tract, so they produce an effect much slower than intravenous ones. And for this reason, intravenous administration is usually preferred in emergency settings and during surgical procedures. On the flip side, oral preparations are much easier to take at home and don’t need any special equipment.

Alright, now each medication is given at a specific schedule or dosing regimen, which determines the frequency of administration, or dosing interval, and the amount administered, known as dose. The regimen is important since it affects the onset of action, or the time it takes for a medication to start working and produce an effect, as well as the duration of action, which is the total length of time during which a medication produces an effect.

So, there are three main types of dosing regimens. First, there’s single dosing, meaning that only one dose of a medication is administered. Let’s plot this into a nice graph with the drug concentration in plasma on the y-axis, and the time on the x-axis. So, with single dosing, the plasma concentration of the medication rises steadily as it gets absorbed into the circulation, until it reaches a peak. Then the concentration drops again, as the medication is distributed into tissues, gets metabolized, and is eliminated.

Next, there’s a regimen of continuous infusion. This is when a medication is infused intravenously at a constant rate. In this case, the plasma concentration progressively rises and reaches a peak, but, instead of falling off, it continues at a plateau, also known as a steady state. The reason why this happens is that as the concentration of the medication increases, so does the rate of elimination, until eventually the dosing and the elimination rate are equal.