Exploring the Different Routes of Drug Administration: An In-Depth Guide


The route of administration is an important aspect of drug delivery. Selecting the right route of administration, or ROA, ensures that the patient’s body can receive and absorb the medication with optimal efficiency and minimal risk of harmful side effects. There are numerous routes of administration, each having its own characteristic attributes, and selection of the ROA is based on the properties of the drug and/or the condition of the patient.

What does route of administration (ROA) mean?

In pharmacology, the route of administration, or ROA, refers to how a drug is delivered into a patient’s body. It is generally determined by the drug’s properties and its pharmacokinetics and pharmacodynamics, but can also depend on the specific condition and state of the patient.

Properties of the drug include its physical and chemical characteristics such as its state (solid, liquid, or gas, which is related to its melting and boiling points), pH, polarity, size, and solubility

Pharmacokinetics (PK) describes what the body does to the drug, i.e.:

  • Where, to what degree, and how quickly it is absorbed
  • How, where, and how quickly it is broken down (metabolized)
  • How it moves throughout the body over time
  • How quickly and in which manner it is excreted from the system

Pharmacodynamics (PD) refers to what the drug does to the body, including how it binds to receptors, what effects it exhibits (including where and for how long it exerts those effects), and what chemical reactions/interactions it is involved in

All of these interconnected factors affect how a drug interacts with the body, and they are so fundamental that the same drug can have different effects depending on its route of administration. For example, naloxone effectively treats opiate overdose when administered via nasal spray. However, if given orally and in low doses, its action is localized to the intestines, making it suitable for treating opioid-induced constipation.

In addition to physical and chemical properties of the drug and its PK and PD, a patient’s condition and physical state, whether related to an illness or not, may also be a factor in selecting the ROA. For example, for someone undergoing a tracheotomy but needing a drug that requires enteral administration, it would have to be administered rectally since the oral route would not be possible (these terms are clarified in the following sections). Because of the complexity and importance of ROA, a drug is normally approved within the context of a specific ROA (although it may also be approved for more than one ROA, usually at different doses and/or in different forms).

How many routes of administration are there?

According to FDA classification, over 100 documented routes of administration are used in healthcare, research, and clinical trials. Note that while the National Curriculum Standards (NCS) prefers the prefix intra-, some routes are described using the endo- prefix, although both prefixes mean within. Each ROA has a specific medical term, abbreviation, FDA code, and NCI ID. Although the list is extensive, there are certainly some primary routes of administration that are used more commonly than others – let’s explore those.

Main routes of administration of drugs

To begin, we can say that there are two main classes of routes of drug administration: enteral and parenteral (relating to whether or not the drug passes through the intestine). These can be divided further according to more specific delivery sites/methods to give the seven most common routes of drug administration: oral, sublingual, rectal, intravenous, intramuscular, subcutaneous, and inhalational.

1. Enteral

Enteral means pertaining to the intestine, and refers to any delivery method whereby the drug passes through the gastrointestinal (GI) tract to reach the bloodstream for a systemic effect. Enteral ROAs include oral, sublingual, and rectal.

It is important to note that the enteral route is affected by first-pass metabolism, which is also known as the first-pass effect. This refers to the liver partially metabolizing (breaking down) the drug before it enters the bloodstream, which typically reduces the concentration of the active drug molecule before it exerts systemic effects (although for some drugs, the active molecule may actually be a metabolite [byproduct of its breakdown], in which case the first-pass effect is actually part of the drug’s action).

Oral (PO)

Oral administration involves taking a drug through the mouth (swallowing). It is commonly abbreviated as PO, meaning per os, the Latin term for ‘by mouth.’ The primary absorption site for drugs taken orally is the small intestine, from where they pass through the gut wall to reach the bloodstream.

The oral route is the most common route of administration as it is cost-effective, painless, and convenient. Oral medications can come in many forms, including liquids, syrups, drops, capsules, and tablets that can be chewed or swallowed. However, first-pass metabolism significantly affects the oral ROA, which may significantly reduce bioavailability. To combat this effect, the dosage is usually increased. While this is viable for some drugs that are well-tolerated and relatively inexpensive to make, it may not suitable for others which would exhibit increased toxicity or which are very expensive.

Other factors that limit oral administration include:

  • The onset of action is slower than other routes of administration.
  • Oral formulations are limited to molecules that can withstand the acidity and numerous enzymes of the stomach
  • This route may lead to gastrointestinal tract irritation, leading to problems like nausea and vomiting

Sublingual (Buccal)

In the sublingual or buccal route, the drug is placed in the mouth but is not swallowed. Rather, the drug is dissolved and absorbed passively through the dense network of capillaries in the mouth, from where it moves into the bloodstream for systemic effect. There is a slight difference between these two routes in terms of the drug’s placement in the oral cavity:

  • Sublingual means under the tongue (denoted as SL)
  • Buccal means between the cheek and gums

Comparatively, drug absorption by sublingual administration is faster than that of the buccal route because the tissue under the tongue is more permeable than that in the cheek.

The sublingual and buccal ROAs have several benefits over oral administration, including:

  • Quicker absorption for faster onset
  • No first-pass metabolism, resulting in higher bioavailability
  • Not subjected to highly acidic stomach conditions and enzymes such as MAO
  • Often easier and more comfortable for a patient (can prevent stomach irritation and nausea)

As a prime example, nitroglycerine tablets are given sublingually because they are absorbed very quickly, relieving chest pain (angina) within minutes. Other drug preparations for sublingual and buccal administration include dissolvable tablets, strips, drops, and sprays. Despite its advantages, the physical properties of the drug can dictate whether or not sublingual/buccal formulations are feasible. Some drugs cannot be absorbed quickly enough through the oral membranes, and will thus simply be diluted by saliva and swallowed.


The rectal route of administration involves the drug being inserted into the rectum, where it is absorbed through a dense network of capillaries. When a drug is administered rectally, some portion of it bypasses first-pass metabolism since the lower part of the rectum is connected directly to systemic circulation. Compared to oral administration, rectal absorption is often slower and less extensive, although some drugs may indeed have a faster onset and higher bioavailability when administered rectally. It has been noted that the specific formulation is very important in this regard; rectal formulations may be in the form of solid tablets (“suppositories”) or liquid solutions, and the excipients (other non-medicinal ingredients) influence the drug’s absorption as well. Other rectal preparations include enemas and specialized rectal catheters. Many medications taken orally also have rectal formulations, which can be used for patients with digestive tract problems such as irritable bowel disorders and obstructions. A well-known example is rectal diazepam gels, which provide near-immediate relief in treating acute seizures.

Rectal administration may be safer than other non-oral routes of administration and has lower associated costs, making it particularly appropriate for palliative care. Additionally, the rectal ROA presents a lower risk of nausea and vomiting as it bypasses the upper GI tract. However, this route of administration is limited by factors such as interruption by defecation, patient discomfort, and drug properties like its solubility.

2. Parenteral

Parenteral administration describes any route of administration that does not pass through the gastrointestinal (GI) tract, with parenteral meaning ‘beside enteral.’ The five most common parenteral routes are intravenous (IV), intramuscular (IM), subcutaneous (SC), intradermal, and intrathecal.

Although often more invasive than enteral administration, the use of injections or catheters leads to significantly higher bioavailability due to avoiding the first-pass effect. Additionally, there are numerous options for administering medications parenterally, depending on whether it is injected directly into the bloodstream, into a muscle, just under the skin, or directly into a specific tissue/organ. This means that nearly all drugs can be administered parenterally, with the desired site of action and properties of the drug determining which specific ROA is most appropriate.

Intravenous (IV)

Intravenous administration (IV) involves injecting the drug into a vein, so the medication enters directly into the bloodstream for a nearly immediate systemic effect. Since bioavailability is defined relative to IV administration, this ROA results in 100% bioavailability. The IV route of administration is the fastest, most effective drug delivery method, and the most common parenteral administration route. It is thus used when immediate effect is required, or when it is important to bypass first-pass metabolism and/or breakdown in the gut, for example with fragile or very expensive molecules.

IV administration can be performed in different variations:

  • IV infusion, which is a slow and prolonged injection, is performed when the medication needs to have a constant blood concentration over a certain period, for example, with antibiotics such as vancomycin and gentamicin
  • By IV bolus, meaning a one-time, large-volume dose for rapid effect, as required with pain relief medication such as morphine
  • With a secondary medication connected to a primary IV infusion, as in the case of chemotherapy, where multiple drugs must be given at one time

A vein in an upper limb is commonly used for the intravenous route of administration. In comparison to veins in lower limbs, they are usually easier to locate due to their superficial location and prominence. Additionally, there is a lower risk of blood clotting problems like thrombosis. Nonetheless, almost any vein can be used, such as the blood vessel network in the sole of the foot, as an example.

Despite its effectiveness, the IV route of administration can lead to discomfort and pain depending on the injection site. Importantly, it must be performed by a trained professional as there is a high risk of inflammation, infection, and leakage into the surrounding tissue around the entry site (known as infiltration, which can be caused by the vein rupturing or incorrect administration). This makes IV administration usually reserved for professional healthcare settings, as it is impractical for home use.

Intramuscular (IM)

In intramuscular administration (IM), the drug is injected into a muscle. Muscles are highly vascular (supplied by blood vessels), so the drug is absorbed directly into the bloodstream. Typical injection sites include larger muscles in the shoulder, upper and outer thigh, and the buttocks – the most common site of IM injection.

The IM route has a slower onset than the IV route, but it is a better parenteral route when controlled absorption is needed, such as for vaccines (especially inactive ones) and hormones such as testosterone.

However, the passive nature of the absorption also means that bioavailability is lower than 100%, which can necessitate higher dosages for certain drugs. Additionally, total injection volume is limited to 2 – 5 mL, depending on the site, and there are several potential side effects, including:

  • Pain, swelling, and redness at and/or around the injection site
  • Nerve and blood vessel damage
  • Localized infections such as gangrene and abscesses if sanitary protocols are not followed

Subcutaneous (SC/SQ)

With subcutaneous meaning ‘under the skin,’ the subcutaneous route of administration (SC, or less commonly SQ) involves delivering the medication to the fatty tissue layer of the skin (the innermost layer of the skin). Preferred entry sites include the outer area of the upper arm, the outer abdomen, the front thigh, the upper buttocks, and the upper back. This layer of the skin has a relatively lower concentration of blood vessels, so the absorption is slower than the IM or IV routes. However, SC injection is preferred for drugs that are most effective in a controlled, sustained way, such as insulin and heparin.

As the parenteral route of administration with the lowest inherent risk, subcutaneous injection is considered relatively safe and can thus be performed by patients themselves, at home, without specialized training. Subcutaneous medications are often delivered via specialized apparatuses with pre-dosed injection volumes and the needle set to a specific injection depth. Regular doses are less than 2 mL, and adverse effects are rare. The most common side effect is injection site reactions, an umbrella term for short-term redness, swelling, and irritation that stays within the vicinity of the delivery site.


In the intranasal route of administration, the drug enters through the nose into its upper cavity (the nasal cavity), which has a dense network of blood vessels behind a thin tissue membrane. Intranasal preparations typically come in either sprays or drops, and drugs administered nasally are absorbed rapidly, typically producing an effect in under 5 minutes.

Intranasal administration can result in local or systemic effects, depending on the drug. For example, decongestant nasal sprays provide local relief for allergies, while migraine nasal sprays offer systemic pain relief.

Although this route is an alternative to oral administration, it is limited by the delicate nature of the nasal tissue, which can be damaged by frequent use. Additionally, only a limited amount of solution can be sprayed inside and absorbed through the nasal cavity; any excess drips down the throat and is swallowed into the GI tract, or may cause upper airway irritation and infection.


The inhalational route of administration takes advantage of the large surface area of the respiratory system, administering drugs in gaseous or aerosol (liquid droplets, or “spray”) form into the upper and central airways. This allows drugs to be rapidly absorbed by the extensive network of blood capillaries for either a localized or systemic effect.

Inhalational preparations of medications can be in the form of mists/sprays, such as corticosteroids for quick reduction of airway inflammation in asthma, and is the most suitable ROA for drugs that are naturally in the gaseous phase, such as nitrous oxide, which is used for moderate pain relief or anesthesia.

A main drawback of the inhalational ROA is that the effects are often shorter in duration. This route of administration is limited by the following factors:

  • The patient’s lung function and capacity determine how much gets into the airway
  • Size of the drug – smaller molecules exhibit better absorption
  • Some compounds cannot be made into gaseous nor aerosol form
  • Formulations may have unpleasant tastes and ingredients that irritate the mouth


Also known as intravaginal, this route of administration involves inserting the drug into the vaginal cavity. Generally, this route is used when a localized effect within the vagina and nearby structures is desired, and is commonly used for contraceptives, artificial insemination, estrogens, progestogens, antibacterials, and antifungals for local treatment.

The intravaginal route is also suitable when systematic effect is desired, because like the other parenteral ROAs, the medication is not digested by the GI tract and there is no first-pass effect. This allows for lower doses with less-frequent administrations, proving to be a safe and effective route for female health-related conditions and hormone therapy. Potential downsides include local irritation of the mucosal membranes, and the drug’s formulation plays a key role as in rectal administration.

Topical and transdermal

In topical and transdermal administration, the drug is placed on the outer layer of the skin. The differentiation between topical and transdermal is based on what happens next; the drug is either absorbed through the skin, over an extended period, to reach deeper tissues and exert systemic effect (transdermal), or penetrates only minimally and mainly exerts its effect locally (topical).

Transdermal patches are used to treat conditions such as tobacco use disorder with nicotine patches, and motion sickness with scopolamine patches. With the recent development of microneedle transdermal patches, lower dosages can be administered due to higher bioavailability. The principal challenge with transdermal administration is that the drug molecules need to be small enough and have the right physical properties to cross multiple layers of skin with different physicochemical properties. It is recommended that consecutive transdermal patches be applied on different sites on the body to minimize local irritation.

Topical ointments, gels, creams, and sprays stay in the vicinity of application for localized treatment, such as pain relief gels containing diclofenac sodium, or retinol ointments for acne treatment. Topical formulations usually have other ingredients to help increase retention, moisturize the skin, or prevent irritation, amongst other possibilities.


Route of administration is a central concept in drug delivery, describing how the drug is given to or taken by the patient. The ROA significantly influences the drug’s bioavailability, metabolism, effects, time of onset, and clearance, and is selected based on a combination of the drug’s physical properties, pharmacokinetics, pharmacodynamics, and the patient’s condition.