Routes of administration and absorption
In the next few steps we will explore the pharmacokinetics of opioids, looking at the routes of administration, absorption, metabolism, excretion and principles of dosing intervals of opioids.
Absorption is the movement of a drug from its site of administration to the bloodstream whilst bioavailability is the fraction of the administered drug which enters the systemic circulation.
First pass metabolism
Most opioids are administered orally and absorbed via the intestine into the hepatic portal circulation. This delivers the parent drug to the liver, where it is metabolised, a phenomenon known as first pass metabolism. Some of the parent drug is lost to elimination during the processes of absorption and first pass metabolism.
Some opioids are poorly absorbed from the gastro-intestinal (GI) tract or are rendered completely inactive by first pass metabolism. This includes diamorphine, fentanyl and alfentanil. These drugs must be administered parenterally (ie by routes other than the intestinal tract). Because the superior haemorrhoidal vein drains into the hepatic portal circulation, rectal administration of opioids does not completely bypass first pass metabolism.
This is the fraction of the parent drug which reaches the systemic circulation. Opioids which are administered parenterally have 100% bioavailability because they do not undergo first pass metabolism.
Oral versus parenteral potency
The difference between oral and parenteral bioavailability of a drug means that the oral dose may not be equivalent to the subcutaneous dose. For instance, 20mg of oral morphine is equivalent to 10mg of morphine injection. This is because 50% of the parent drug is lost to first pass metabolism when taken orally.
Modified release oral opioids
The absorption of these opioids from the GI tract is slower than immediate release formulations of the same drug. Modified release (MR) preparations extend the time it takes for the drug to be released. For most opioids this is over 12 hours. The drug still undergoes first pass metabolism.
Avoiding first pass metabolism
The following routes of administration bypass first pass metabolism:
For the vast majority of patients with chronic, cancer pain where oral opioids are not an option, subcutaneous injection is preferred. This is because it is more predicatable, less invasive and better tolerated than intravenous and intramuscular routes. Intramuscular absorption is dependent on the vascularity of the site and can be painful. Drugs can be continuously infused via subcutaneous and intravenous routes.
Administering opioids by the transdermal route enables very lengthy modified release whilst also avoiding first pass metabolism. This route is only suitable for pain which has already been stabilised and well controlled with opioids via another route. The transdermal route is influenced by skin perfusion and physical adherence of the patch.
Transmucosal membranes are permeable and have a rich blood supply. Opioids that are administered in this way (nasal, sublingual and buccal) rapidly enter the systemic circulation. However, their duration of action is very short and complex administration routines may be difficult for some people to follow.
In the next step we will look at opioid metabolism.
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