Routes of Administration

Two important concepts:

Bioavailability

• The amount of drug administered that is available to the body

• Bioavailability of IV (intravenous) medications is 100% (1.o)

First Pass Effect

Medications administered orally are absorbed through stomach and intestines. Blood from the intestines flows through the liver which allows metabolism of the drug prior to entering systemic circulation.  Other factors influencing first pass metabolism are gut lumen enzymes, bacterial enzymes, and intestinal wall enzymes.

Administration Routes

Oral

In oral administration, the drug is administered by mouth and swallowed.  While this is the most common method of drug administration, the numerous factors involved in getting the drug into the body's circulation make this a complex method of delivery.

Enteric Coating

The drug must be able to tolerate the stomach's low pH. If the drug is unable to tolerate the stomach's pH, enteric coating can be applied to drugs to allow drug to pass through the stomach to the small intestine prior to being available for absorption.  Some drugs can be absorbed directly through the stomach.

Enteric coating can also be used to protect the stomach from drugs that are irritating to the stomach lining.

Extended-Release Formulations

Extended-release formulations require less frequent dosing than immediate release drugs.  Result in fewer highs (peaks) and lows (troughs) of drug concentration level.

First Pass Metabolism

Many drugs are subject to first pass metabolism during absorption through the GI tract and passage through the portal circulation and liver.  First pass metabolism can result in significant portion of the drug being metabolized prior to reaching systemic circulation.

Sublingual or Buccal

In sublingual and buccal administration, the drug is held in mouth until absorbed.  The drug is absorbed directly into the capillary network of the mucosa and distributed in the systemic circulation.  This method avoids first pass metabolism and harsh stomach environment. Used commonly in patients with vomiting.

Parenteral

Parenteral administration includes drugs that are administered IV (intravenously), IM (intramuscularly), or SQ (subcutaneously). Administration parenterally provides several advantages:

• Increases control of timing of drug delivery - slow GI transit, vomiting, or diarrhea are bypassed

• Known amount of drug delivery

• Drug not exposed to enteral environment

• Avoids first pass metabolism

IV Administration

IV administration can occur in two methods: bolus and infusion.

• Bolus - drug is administered rapidly over a short period of time (seconds to minutes). Drug effects are seen rapidly with this method of administration.

• Infusion - drug is administered continuously over a longer duration (minutes to hours). Plasma concentrations are more constant with this method of administration. A loading dose is sometimes used at the beginning of an infusion to reach a therapeutic drug level rapidly.

IM Administration

Drugs administered via the IM route are absorbed rapidly by diffusion unless prepared in depot or sustained-release formulation.  

Depot or sustained-release formulations assist with drug compliance as less frequent dosing is necessary (mental health, birth control, etc.)

SQ Administration

Intramuscular administration is important when IV access is not available/necessary/safe but oral administration is not desired/possible.

Absorbed by diffusion. Tends to allow for constant and relatively slow drug effects.  Insulin is primarily given via the subcutaneous route.

Inhalation

The drug is inhaled through the mouth and/or nose and delivered to respiratory and mucus membranes of the mouth, nose, throat, bronchioles, and lungs.

There are two main advantages to inhalation:

• Drug delivered to site of action

Nebulized lidocaine for local anesthesia 

• Bronchodilators for asthma/COPD treatment

• Limits systemic side effects

• Absorbed quickly

Intrathecal or Intraventricular

Drug administered directly into the CNS. This method is used for drugs that have a difficult time crossing the blood-brain barrier and when localized treatment desired.

Topical

Drug applied to the surface of the skin or eyes for local effect. Generally limited systemic effects.

Transdermal

Drug absorbed through the skin/dermis into systemic circulation.  Transdermal administration allows for sustained drug levels (nitroglycerin patches, nicotine patches, etc.).

Rectal

Drug is inserted into the rectum and bypasses most first pass metabolism. Rectal administration is useful in situations when vomiting or difficulty swallowing does not allow for oral administration (stroke, vomiting, etc.). Some patients find this method of administration unpleasant.