1.3 Pharmacokinetics — Absorption V2

Pharmacokinetics

Pharmacokinetics is the term that describes the four stages of absorption, distribution, metabolism, and excretion of drugs. Drugs are medications or other substances that have a physiological effect when introduced to the body.

There are four basic stages for a medication to go through within the human body:

1. Absorption occurs after medications enter the body and travel from the site of administration into the body’s circulation.
2. Distribution is the process by which medication is distributed throughout the body.
3. Metabolism is the breakdown of a drug molecule.
4. Excretion is the elimination of the medication from the body.

This entire process is sometimes abbreviated as ADME.

Absorption

The first stage of pharmacokinetics is known as absorption. Absorption is defined as the movement of the drug from its site of administration into the blood (Burcham & Rosenthal, 2019). Most drugs must be absorbed to produce an effect, with a few exceptions such as intestinal anti-infectives. The amount of absorption will determine how intense the effects will be, and the rate of absorption will determine how soon the effects will occur.

Drug absorption is impacted by a number of factors including the physical properties of the drug and the physiologic factors at the absorption site. For example, the formulation of the drug, either a tablet or liquid, determines the rate of absorption. An oral drug that is given in a tablet form must be dissolved before being absorbed, which delays absorption; whereas a liquid form of that drug does not need to dissolve will therefore have a faster absorption rate. Physiologic factors include the surface area (small intestine has a huge surface area compared to the stomach), blood flow (areas of high blood flow will absorb drugs more rapidly), lipid solubility, and pH levels. While most drugs need to be absorbed first before entering the bloodstream enroute to the target site, not all drugs do. For example, antacids are given orally and exert their actions locally in the stomach.

Absorption affects the speed and concentration at which a drug may arrive at its desired or target site. Each administration route has its own absorption characteristics, advantages, and disadvantages. The route chosen will depend on the desired effect and the type of drug preparations available. Depending on the intended response, the route is chosen based on the speed of response required (for example, the IV route is preferred for fast pain relief), duration of action, or other factors such as convenience, availability, and client factors.

Routes of Administration

Medications can enter the body through various routes of administration. The routes of administration are often divided into two major groups:

1. Enteral, meaning through the gastrointestinal (GI) tract, includes all oral and rectal medications.
2. Parenteral, literally meaning outside the GI tract but refers to by injection, includes intravenous, subcutaneous, intramuscular, intrathecally, and intra-articular medications.

Common routes to administer medications include:

• Oral (swallowing an aspirin tablet),
• Sublingual (dissolved under the tongue),
• Enteral (administering to the GI tract such as via a nasogastric tube),
• Rectal (administering a Tylenol suppository),
• Inhalation (breathing in medication from an inhaler),
• Intramuscular (getting a flu shot in the deltoid muscle),
• Subcutaneous (injecting insulin into the fat tissue beneath the skin), and
• Transdermal (wearing a nicotine patch).

Characteristics of Routes of Administration

A new graduate nurse is planning on giving a client their medication and sees the prescriber orders have a few different routes for some of the medications. Which route should the nurse choose? What factors of the route, client, or intended effect would make one route more ideal than another?

Each route has advantages and challenges that can impact the effectiveness or are not as ideal for that client. The nurse uses the nursing process and clinical judgment in making the decision of which route to use when given the option. Depending on the orders, the nurse can decide to give a medication orally, IM, or IV. For example, the IV route requires the nurse to start an IV, which can be painful but IV meds have a rapid onset of action. In an emergency, rapid onset of action is highly important. If we need a more prolonged effect, IM might be the best option, but it can also be painful. If the client is able to tolerate an oral medication and its not an emergency, the oral route might be best due to its convenience.

Refer to the Table 1.3.2 for a review of route characteristics. The oral route will be examined more thoroughly below.

Oral Administration

The most common route of administration is the oral, or enteral, route. The drug is absorbed into the systemic circulation through the gastric mucosa, either in the stomach or small intestine. If given rectally, it is readily absorbed through the rectal mucosa.

Advantages of the oral route include convenience, affordable (compared to IV), and easy administration for most clients. The old saying, “if the gut works, use it,” would apply when choosing oral medications over IV ones. Other advantages are that the oral route has a high safety margin compared to IV routes, which could risk infection or fluid overload. It may also be possible to reverse an oral medication in the case of an overdose. If the medication was recently ingested, giving activated charcoal will bind with the medication to prevent absorption.

A workaround for the first-pass effect is to administer the medication using alternate routes, such as dermal, nasal, inhalation, subcutaneous, intramuscular, or intravenous. Alternative routes of medication administration bypass the first-pass effect by entering the bloodstream directly or via absorption through the skin or lungs. Intravenous medications administered directly into the bloodstream do not undergo absorption and are fully available for distribution to tissues within the body. Inhaling drugs through the nose or mouth is another alternative route for rapid medication delivery that bypasses the liver. For example, metered-dose inhalers have been a mainstay of asthma therapy for several years, and nasal steroid medications are often prescribed for allergy and sinus problems.

Transdermal application of medication is an alternate route that has the primary benefit of slow, steady drug delivery directly to the bloodstream—without passing through the liver first.  (See Figure 1.3d for an image of applying a transdermal patch.)

Bioavailability

Bioavailability is the extent of drug absorption and is the fraction of the originally administered drug that arrives in systemic circulation. It plays a critical role in achieving the desired therapeutic effects. It is affected by many factors, including the properties of the drug, the mode of administration, interactions with other substances (food, fluids, other drugs), absorption (status and blood flow to small intestine), hepatic metabolism, and excretion (Stielow et al., 2023). For example, a client with gastric paresis post-operatively will slow the transit time through the gut.

A drug administered via the IV route, which bypasses the absorption phase, will have 100% of the drug arriving in the bloodstream. It is a fast delivery of the drug, and all of the drug dosage is delivered to the site, leading to 100% bioavailability. Orally administered drugs will have much lower bioavailability, as they must first go through the absorption phase and then be processed by digestive enzymes and the liver, which subsequently lowers the amount of drug that arrives in circulation. An example of a medication with low bioavailability is oral nitrates. Most routes have lower bioavailability than the gold standard of the IV route of administration. If two medications have the same bioavailability and also the same concentration of the active ingredient, then they are considered bioequivalent.

Two phrases are often heard when discussing bioavailability:

• Bioequivalent is if two medications given to the same client in the same dosage (concentration of active ingredient) result in equivalent concentrations of the drug in the plasma and tissues.
• Therapeutic equivalence is a step further and indicates that two medications given to the same client in the same dosage will have the same therapeutic and adverse effects.

It is expected that bioequivalent drugs are therapeutically equivalent. These terms are heard when comparing a generic drug with a brand-name drug.

Oral Medication Preparations

The route of the medication is not the only consideration when planning on giving an oral medication. The nurse must also check for how the med is ‘packaged’ or formulated. This applies to oral medication types like tablets or capsules. More specifically, they include enteric-coated, delayed-release, controlled-release, and sustained-release medications. Each type has different implications for the intensity of effect and duration of action (see Table 1.3.1), and impacts when the nurse will reassess for onset of action and monitoring for effects.

The Impact of Food on Absorption

Depending on the drug, you might see in the orders to give the medication with milk, without food, or even after a window of time where no food or drink can be taken. This is often ordered due to the impact on the absorption of that drug. Pay attention to these orders, for if they are not followed, clients may not be getting the ordered dose of that med or it can delay the onset of action leading to negative client outcomes.

There are many examples of drug-food interactions:

• Tetracycline, an antibiotic, cannot be given with food that contains calcium, iron, or magnesium, which can all delay absorption. It is best to take this antibiotic on an empty stomach.
• Levothyroxine, a thyroid medication, or lithium, a mood stabilizer, should not be taken with milk. Dairy products can bind with these drugs to make them ineffective. Ideally, take this medication on an empty stomach.
• Simvastatin, a cholesterol lowering medication, should not be taken with grapefruit juice. The juice will block with enzymes that metabolize the drug, leading to higher drug amounts and stronger effects. There are many meds that should not be taken with grapefruit. See the “Metabolism” unit for more details.

Table 1.3.2 Medication Route Considerations 

Medication Route	Considerations
Oral (PO), Sublingual (SL) or Enteral (NGT, GT, OGT) Ingestion	Oral route (PO), Enteral Convenient, easy, and safest route Highly variable rate and extent of absorption due to acidity of gastric contents, gastric emptying rate, dietary contents, and presence of other drugs (can interact with other drugs) First-pass effect: Blood containing the absorbed drug passes through the liver, which can deactivate a substantial amount of the drug and decrease its bioavailability (the percentage of dose that reaches the systemic circulation). Oral route: different formulations including enteric-coated, extended release. Sublingual/Buccal: More rapid absorption than oral, as it avoids the first-pass effect by avoiding the stomach. Clients need to be taught not to swallow SL medications and instead place it under their tongues. Buccal route medications are placed between cheek and gums.
Rectal (PR)	Rectal: Rapid absorption and a good alternative if oral route not feasible due to secondary issues such as nausea, vomiting, sedation, or NPO Local and systemic effects Mixed first-pass effect and non-first-pass effect (PR bypasses 2/3 of first-pass effect so bioavailability is less of an impact) May cause discomfort and be more embarrassing for client
Parenteral Injection (SC, IM, IV)	Subcutaneous (SQ) and intramuscular (IM) administration: Pharmacokinetics are nearly identical for SQ and IM. Once injected, they readily enter bloodstream SQ: Good for medications that need slow, sustained absorption Injected under epidermis into fat and connective tissue beneath the dermis, so there is less blood flow and slower absorption Good for insulin and palliative pain control IM: Good for poorly soluble drugs (depot drugs). More immediate onset compared  to oral routes. Rate of absorption varies due to blood flow to muscle and water solubility of drug (i.e., high water solubility = faster absorption) SQ and IM: Discomfort at injection site, inconvenient, and risk of bruising, infection, local irritation, or injury Self-administering may be difficult for clients Intravenous (IV): Rapid onset (drug immediately enters bloodstream) so complete bioavailability, better control over the amount of drug, large volumes of fluid, can give irritating drugs to running IV, and avoids first-pass effect Need intravenous access, which can be painful and increase risk of infection Must be careful with two IV meds to avoid incompatibility. Higher risk of toxicity and medication errors due to incorrect administration (dilution, concentration, rate of delivery, and monitoring). More costly, inconvenient, inability to retrieve the medication once given, and risk of embolism and fluid overload
Pulmonary Inhalation	Inhalation: Rapid absorption of drugs in gaseous, vaporized, or aerosol form. Drug delivered directly to lung tissues where most of these drugs exert their action. Absorption of particulates/aerosols depends on particle/droplet size, which influences depth of entry through the pulmonary tree to reach the alveoli. The ability of the client to create successful inhalation, especially in the presence of bronchospasm, may also influence depth of entry in the pulmonary tree. Administration technique is important (use of spacers, nebulizers, or discs may be confusing) Need to correctly store and clean devices
Topical and Transdermal Application	Topical creams, lotions, and ointments: Generally used for local effect; minimal/no systemic effects Easy to administer Slower absorption through skin but has a steady, long-term effect that avoids first-pass effect Absorption affected by blood flow Transdermal patch: Used for systemic effect. Constant rate of drug absorption and avoids first-pass effect Long term effects last up to 7 days Absorption can be affected by perspiration and body temperature More costly, may cause skin irritation, and need safe disposal of patch

Researchers who specialize in pharmacokinetics must also pay attention to another dimension of drug action within the body: time. Unfortunately, scientists do not have the ability to actually see where a drug is going or how long it is active. To compensate, they use mathematical models and precise measurements of blood and urine to determine where a drug goes and how much of the drug (or breakdown product) remains after the body processes it. Other indicators, such as blood levels of liver enzymes, can help predict how much of a drug is going to be absorbed.

Principles of chemistry are also applied while studying pharmacokinetics because the interactions between drugs and body molecules are really just a series of chemical reactions. Understanding the chemical encounters between drugs and biological environments, such as the bloodstream and the oily surfaces of cells, is necessary to predict how much of a drug will be metabolized by the body.

Learning Activities

References

Burcham, J. R., & Rosenthal, L. (2019). Lehne’s pharmacology for nursing care (10^th ed). Elsevier.

Doyle, G. R., & McCutcheon, J. A. (2015). 6.7 Administering topical medication. In Clinical procedures for safer patient care. BCcampus. https://opentextbc.ca/clinicalskills/chapter/administering-topical-medication/. Download this book for free at http://open.bccampus.ca.

Polaka, S., Tella., J. D., Tekade, M., Sharma, M., & Tekade, R. K. (2022). Chapter 10 – Impact of ageing on pharmacokinetics and pharmacodynamics of the drugs. In R. K. Tekade (Ed.), Pharmacokinetics and toxicokinetic considerations (p. 241-261). Academic Press. https://doi.org/10.1016/B978-0-323-98367-9.00008-1

Stielow, M., Witczyńska, A., Kubryń, N., Fijałkowski, Ł., Nowaczyk, J., & Nowaczyk, A. (2023). The bioavailability of drugs—The current state of knowledge. Molecules, 28(24), Article 8038. https://doi.org/10.3390/molecules28248038

Media Attributions

• Symbol lightbulb by CheChe, via Wikimedia Commons, is used under a CC BY-SA 4.0 license.
• Generic Brands Same Quality and Performance by U.S. Food and Drug Administration, in the public domain.
• Figure 1.3a A drug’s life in the body (with labels) | Medicines taken by NIH Image Gallery, via Flickr, is used under a CC BY-NC 2.0 license.
• Figure 1.3b Person Holding White Medication Pills by Ahsanjaya, via Pexels, is used under the Pexels License.
• Figure 1.3c Applying Transdermal Patch by Glynda Rees Doyle and Jodie Anita McCutcheon (2015), via BCIT’s Clinical Procedures for Safer Patient Care, is used under a CC BY 4.0 license.
• Figure 1.3d Plasma level time curves for different types of drug administration is from Stielow et al. (2023), and is used under the MDPI Open Access terms.
• Figure 1.3e A comparison of brand name and generic medications is by Sheila Odubote and is subject to the CC BY NC SA license.
• Figure 1.3f Plasma concentration over time for different drug-release formulations is by TRU Open Press and is subject to the CC BY NC SA license.
• Table 1.3g:
• Figure 1.3h Administering oral medication by Glynda Rees Doyle and Jodie Anita McCutcheon (2015), via BCIT’s Clinical Procedures for Safer Patient Care, is used under the CC BY 4.0 license.
• Figure 1.3i Administering-med-rectally-2 [Figure 6.1] by Glynda Rees Doyle and Jodie Anita McCutcheon (2015), via BCIT’s Clinical Procedures for Safer Patient Care, is used under the CC BY 4.0 license.
• Figure 1.3j Subcutaneous (SQ) and intramuscular (IM) administration by National Cancer Institute, via Unsplash, is used under the Unsplash License.
• Figure 1.3k Adult Using an Asthma Inhaler (29251369035) by National Institute of Allergy and Infectious Diseases (NIAID), via Flickr, is used under a CC BY 2.0 license.
• Figure 1.3l Applying Transdermal Patch by Glynda Rees Doyle and Jodie Anita McCutcheon (2015), BCIT’s Clinical Procedures for Safer Patient Care, is used under a CC BY 4.0 license.