Pharmacokinetics is the study of how the body works on or affects a drug once it has been administered. This is different to pharmacodynamics which is the study of how a drug affects the body. Pharmacokinetics refers to the body's affect on the drug.

Depending on which literature you read, there are at least four main phases of pharmacokinetics.

  • Absorption
  • Distribution
  • Metabolism
  • Excretion

Routes or Modes of administration

Before we delve into the phases of pharmacokinetics, we need to look at the different modes or routes of administration.

The main modes of administration that we are familiar with as paramedics are intramuscular, intravenous, intranasal and oral. Oral can be sublingual, buccal or swallowed into the GI tract. There are other modes of administration such as transcutaneous (skin patches), subcutaneous (under the skin but not intra-muscular) and parenteral (rectal) but they are not as common in paramedicine. As we will see, the mode of administration can affect the bioavailability of a drug.

Bioavailability is simply the amount of drug that reaches its target site in the body after it has been administered.


The absorption of a drug refers to how the molecules of that drug make their way to the blood stream after being administered.

The route or mode of administration can alter the absorption process, sometimes reducing the overall amount of drug that is available or the time that the drug takes to reach therapeutic levels.


Intramuscular (IM) administration will allow for therapeutic levels within a few minutes and will generally allow for the entire volume of the drug to take effect. The drug is first absorbed into the muscle tissue and then makes its way into the blood stream through diffusion from muscle cells into the capillaries. IM avoids the hepatic first pass, meaning that the drug circulates though the blood stream before it is metabolised by the liver, allowing for the entire drug to take effect.


Intravenous (IV) administration is a common and familiar route of administration for Paramedics. We wont cover intravenous cannulation in this session, but vascular access is obviously and important intervention to have performed prior to administering a drug intravenously! IV administration allows a drug to take effect very quickly, in some cases within seconds. This is the most direct form of administration for most dugs and requires that a drug has been appropriately prepared for IV administration. Not all drugs are suitable for IV administration and you should never attempt to use any drugs that are not prepared for IV use. IV administration also bypasses the hepatic first pass.


Intranasal refers to the administration of a drug, generally in liquid form, into the nasal passages where it diffuses rapidly through the nasal mucosa and into the blood stream. Commonly, the liquid form will be atomised into a fine mist, which will encourage the drug to cling to the nasal mucosa and absorb. It is not common practice in paramedicine to administer drugs intranasally in a powdered form as we see in the movies! IN administration also avoids the hepatic first pass.

Oral (Sublingual and Buccal)

Sublingual, meaning “below the tongue”, refers to a drug that dissolves in saliva under the tongue. Generally, these drugs are manufactures in such a way that they dissolve quickly and can be in tablet/wafer form, drops or liquid and a spray. SL drugs absorb quickly into the oral mucosa and make their way directly to the blood stream, also avoiding the hepatic first pass.

Saliva is 99.9% water and contains enzymes such as Amylase and Lipase which help to begin digestion of carbohydrates/starches and lipids. The pH of saliva is relatively neutral at 6.3.

Oral (GI Tract (Enteral))

The GI tract is different to most other modes of administration in that it involves the hepatic first pass and due to its function, generally results in a prolonged absorption time. This can make it unsuitable for immediate or critical care, especially cardiac drugs and analgesia. For many oral drugs administered via the GI tract,, the onset of action can be up to 20-30 minutes with peak serum levels and therapeutic effect ranging between 30 minutes to over an hour. For example, Paracetamol is usually effective within 45 minutes of oral administration via the GI tract.

Some drugs begin to absorb in the stomach, but most drugs will absorb in the intestinal system. For example, alcohol is absorbed in the stomach, which is why it seems to affect people very quickly in large amounts. Some medications are designed to digest slowly and will have an enteric coating that means the drug and its excipients disperse through the intestinal system over a longer period. These drugs will not break down in the stomach and will be resistant to the low pH of the upper GI tract.

Since the hepatic first pass is involved, this means that some of the drug is processed by the liver immediately after entering the blood stream which can result in a varied bioavailability of that drug when compared to an IV administration. For example, 100mg of a drug ingested, might only yield 60mg of that drug being bioavailable.


Distribution refers to how the molecules of the drug are transported through fluids and tissues of the body to their target site. There are four main compartments that the drug can be distributed to as well as some minor compartments.

  • Blood
  • Intracellular Fluid
  • Extracellular Fluid
  • Fat

Some definitions:

  • Hydrophilic: Easily attaches to, or dissolves in water molecules
  • Hydrophobic: Does not attach to, or dissolve in water molecules
  • Lipophilic: Easily attaches to, ot dissolves in lipids (fats)
  • Lipophobic: Does not attach to, or dissolve in lipids

Plasma Protein Binding

Tissue Distribution

The Blood Brain Barrier (BBB)


Specifically, xenobiotic metabolism, is the process of transforming the drug molecule from a lipid soluble form, into water soluble form through enzymatic reactions. This results in smaller compounds known as metabolites. One common xenobiotic enzyme is cytochrome P450 which is used to metabolise nearly every drug or poison that enters the body. Xenobiotic metabolism is one of many metabolic pathways in the body, but unlike most other pathways, it acts on foreign molecules that do not participate in catabolic or anabolic processes.

The product of xenobiotic metabolism is metabolites and a reduction of circulating drug. Imagine a racetrack with lots of cars racing around it. Every now and then a car gets pulled off the track and split into parts. It now can’t participate in the race so there are less cars on the track. Metabolism acts in a similar fashion. The liver can only deal with so many molecules at one time, so not every molecule gets processed each time it passes through. The administration, absorption, distribution and volume of drug, among other factors, will affect the time and nature of how each drug is metabolised.

Drug metabolism works in two phases.

Phase 1: A chemical process that generally involves cytochrome P450. Usually an enzyme driven, oxidative process that produces pharmacologically inactive metabolites

Phase 2: The process of combining metabolites with a substrate that produces a water soluble, inactive conjugate that can be easily excreted from the body.


The removal of the metabolites from the body, generally by the kidneys. Because the metabolites are converted into a water soluble form, they are easily removed in the urine. Some drugs can be excreted in faecal matter or through the lungs as expired air.


Page contributors:


Chris Gray, AP20186
Ambulance Paramedic, Metropolitan Ambulance Service

Want to help improve this article? Visit our Contribute page.

Clinical Resources Website

St John Ambulance Western Australia Ltd (ABN 55 028 468 715) (St John WA) operates ambulance and other pre-hospital clinical services. St John WA’s Clinical Resources, including its Clinical Practice Guidelines (Clinical Resources), are intended for use by credentialed St John WA staff and volunteers when providing clinical care to patients for or on behalf of St John WA, within the St John WA Clinical Governance Framework, and only to the extent of the clinician’s authority to practice.

Other users – Terms of Use

The content of the St John WA Clinical Resources is provided for information purposes only and is not intended to serve as health, medical or treatment advice. Any user of this website agrees to be bound by these Terms of Use in their use of the Clinical Resources.

St John WA does not represent or warrant (whether express, implied, statutory, or otherwise) that the content of the Clinical Resources is accurate, reliable, up-to-date, complete or that the information contained is suitable for your needs or for any particular purpose. You are responsible for assessing whether the information is accurate, reliable, up-to-date, authentic, relevant, or complete and where appropriate, seek independent professional advice.

St John WA expressly prohibits use of these Clinical Resources to guide clinical care of patients by organisations external to St John WA, except where these organisations have been directly engaged by St John WA to provide services. Any use of the Clinical Resources, with St John WA approval, must attribute St John WA as the creator of the Clinical Resources and include the copyright notice and (where reasonably practicable) provide a URL/hyperlink to the St John WA Clinical Resources website. 

No permission or licence is granted to reproduce, make commercial use of, adapt, modify or create derivative works from these Clinical Resources. For permissions beyond the scope of these Terms of Use, including a commercial licence, please contact medservices@stjohnambulance.com.au

Where links are provided to resources on external websites, St John WA:

  • Gives no assurances about the quality, accuracy or relevance of material on any linked site;
  • Accepts no legal responsibility regarding the accuracy and reliability of external material; and
  • Does not endorse any material, associated organisation, product or service on other sites.

Your use of any external website is governed by the terms of that website, including any authorisation, requirement or licence for use of the material on that website.

To the maximum extent permitted by law, St John WA excludes liability (including liability in negligence) for any direct, special, indirect, incidental, consequential, punitive, exemplary or other loss, cost, damage or expense arising out of, or in connection with, use or reliance on the Clinical Resources (including without limitation any interference with or damage to a user’s computer, device, software or data occurring in connection with such use).


Please read this cookie policy carefully before using Clinical Resources from St John WA.

The cookies used on this site are small and completely anonymous pieces of information and are stored on your computer or mobile device. The data that the cookies contain identify your user preferences (such as your preferred text size, scope / skill level preference and Colour Assist mode, among other user settings) so that they can be recalled the next time that you visit a page within Clinical Resources. These cookies are necessary to offer you the best and most efficient possible experience when accessing and navigating through our website and using its features. These cookies do not collect or send analytical information back to St John WA.

Clinical Resources does integrate with Google Analytics and any cookies associated with this service enable us (and third-party services) to collect aggregated data for statistical purposes on how our visitors use this website. These cookies do not contain personal information such as names and email addresses and are used to help us improve your user experience of the website.

If you want to restrict or block the cookies that are set by our website, you can do so through your browser setting. Alternatively, you can visit www.internetcookies.com, which contains comprehensive information on how to do this on a wide variety of browsers and devices. You will find general information about cookies and details on how to delete cookies from your device. If you have any questions about this policy or our use of cookies, please contact us.

St John Ambulance Western Australia Ltd © Copyright 2020, All Rights Reserved

Terms of Use | Privacy Policy | Copyright Statement & Disclaimer