Editing Route of administration

{{short description|Path by which a drug, fluid, poison, or other substance is taken into the body}}
[[File:120310-F-XC314-001 (6979611329).jpg|thumb|Oral administration of a liquid.]]
In [[pharmacology]] and [[toxicology]], a '''route of administration''' is the way by which a [[medication|drug]], fluid, poison, or other substance is taken into the body.<ref>[http://medical-dictionary.thefreedictionary.com/route+of+administration TheFreeDictionary.com > route of administration] {{Webarchive|url=https://web.archive.org/web/20110612045450/http://medical-dictionary.thefreedictionary.com/route+of+administration |date=2011-06-12 }} Citing: Jonas: Mosby's Dictionary of Complementary and Alternative Medicine. 2005, Elsevier.</ref>

Routes of administration are generally classified by the  location at which the substance is applied.  Common examples include [[oral administration|oral]] and [[intravenous therapy|intravenous]] administration. Routes can also be classified based on where the target of action is.  Action may be [[topical medication|topical]] (local), [[enteral administration|enteral]] (system-wide effect, but delivered through the [[gastrointestinal tract]]), or [[#Parenteral|parenteral]] (systemic action, but is delivered by routes other than the GI tract). Route of administration and [[dosage form]] are aspects of [[drug delivery]].

==Classification==
Routes of administration are usually classified by application location (or exposition).

The route or course the active substance takes from application location to the location where it has its target effect is usually rather a matter of [[pharmacokinetics]] (concerning the processes of uptake, distribution, and elimination of drugs). Exceptions include the [[transdermal]] or transmucosal routes, which are still commonly referred to as ''routes of administration''.

The location of the target effect of active substances is usually rather a matter of [[pharmacodynamics]] (concerning, for example, the physiological effects of drugs<ref>{{cite journal |vauthors=Lees P, Cunningham FM, Elliott J |title=Principles of pharmacodynamics and their applications in veterinary pharmacology |journal=J. Vet. Pharmacol. Ther. |volume=27 |issue=6 |pages=397–414 |year=2004 |pmid=15601436 |doi=10.1111/j.1365-2885.2004.00620.x |url=http://researchonline.rvc.ac.uk/id/eprint/912/ |access-date=2023-12-09 |archive-date=2022-08-18 |archive-url=https://web.archive.org/web/20220818044753/https://researchonline.rvc.ac.uk/id/eprint/912/ |url-status=live }}</ref>). An exception is [[topical medication|topical administration]], which generally means that both the application location and the effect thereof is local.<ref name="mw-topical">{{cite web|url=https://www.merriam-webster.com/dictionary/topical|title=topical|website=[[Merriam-Webster]] dictionary|access-date=2017-07-30|archive-url=https://web.archive.org/web/20170730223343/https://www.merriam-webster.com/dictionary/topical|archive-date=2017-07-30|url-status=live}}</ref>

[[Topical medication|Topical administration]] is sometimes defined as both a local application location and local [[pharmacodynamic]] effect,<ref name="mw-topical"/> and sometimes merely as a local application location regardless of location of the effects.<ref name=freedict-topical>[http://www.thefreedictionary.com/topical thefreedictionary.com > topical] {{Webarchive|url=https://web.archive.org/web/20101205213439/http://www.thefreedictionary.com/topical |date=2010-12-05 }} Citing: The American Heritage Dictionary of the English Language, Fourth Edition, 2000</ref><ref name=dict-topical>{{cite web|url=http://www.dictionary.com/browse/topical|title=topical|website=dictionary.com|access-date=2017-07-30|archive-url=https://web.archive.org/web/20170730214617/http://www.dictionary.com/browse/topical|archive-date=2017-07-30|url-status=live}}</ref>

===By application location===
====Enteral/gastrointestinal route====
Through the [[gastrointestinal tract]] is sometimes termed ''enteral or enteric administration'' (literally meaning 'through the [[intestines]]'). ''Enteral/enteric administration'' usually includes ''[[oral administration|oral]]''<ref name="url195_20-1-3.1.htm"/> (through the [[Human mouth|mouth]]) and ''[[Rectal (medicine)|rectal]]'' (into the [[rectum]])<ref name="url195_20-1-3.1.htm">{{cite web |url=http://www.oar.state.ok.us/viewhtml/195_20-1-3.1.htm |title=Oklahoma Administrative Code and Register > 195:20-1-3.1. Pediatric conscious sedation utilizing enteral methods (oral, rectal, sublingual) |access-date=2009-01-18 |archive-url=https://web.archive.org/web/20110722120920/http://www.oar.state.ok.us/viewhtml/195_20-1-3.1.htm |archive-date=2011-07-22 |url-status=live }}</ref> administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may also occur already in the [[stomach]], and as such ''gastrointestinal'' (along the [[gastrointestinal tract]]) may be a more fitting term for this route of administration. Furthermore, some application locations often classified as ''enteral'', such as [[sublingual administration|sublingual]]<ref name="url195_20-1-3.1.htm"/> (under the tongue) and [[sublabial administration|sublabial]] or [[Buccal administration|buccal]] (between the cheek and gums/[[gingiva]]), are taken up in the proximal part of the [[gastrointestinal tract]] without reaching the intestines. Strictly [[enteral administration]] (directly into the intestines) can be used for systemic administration, as well as local (sometimes termed [[topical]]), such as in a contrast [[enema]], whereby contrast media are infused into the intestines for imaging. However, for the purposes of classification based on location of effects, the term enteral is reserved for substances with systemic effects.

[[File:Administering medication into a gastric tube.jpg|thumb|A medical professional injects medication into a gastric tube.]]
Many drugs as [[Tablet (pharmacy)|tablets]], [[Capsule (pharmacy)|capsules]], or drops are taken orally. Administration methods directly into the stomach include those by [[gastric feeding tube]] or [[gastrostomy]]. Substances may also be placed into the [[small intestine]]s, as with a [[duodenal]] feeding tube and [[enteral administration|enteral nutrition]]. Enteric coated tablets are designed to dissolve in the intestine, not the stomach, because the drug present in the tablet causes irritation in the stomach.
[[File:Administering-med-rectally-2.png|thumb|Administering medication rectally]]
The [[rectal]] route is an effective route of administration for many medications, especially those used at the [[end-of-life care|end of life]].<ref>{{cite journal |vauthors=Davis MP, Walsh D, LeGrand SB, Naughton M | year = 2002 | title = Symptom control in cancer patients: the clinical pharmacology and therapeutic role of suppositories and rectal suspensions | journal = Support Care Cancer | volume = 10 | issue = 2| pages = 117–38 | doi=10.1007/s00520-001-0311-6| pmid = 11862502 | s2cid = 30569818 }}</ref><ref>{{cite journal |vauthors=De Boer AG, Moolenaar F, de Leede LG, Breimer DD | year = 1982 | title = Rectal drug administration: clinical pharmacokinetic considerations | journal = Clin Pharmacokinetics | volume = 7 | issue = 4| pages = 285–311 | doi=10.2165/00003088-198207040-00002 | pmid=6126289| s2cid = 41562861 }}</ref><ref>{{cite journal |vauthors=Van Hoogdalem EJ, de Boer AG, Breimer DD | year = 1991 | title = Pharmacokinetics of rectal drug administration, Part 1 | journal = Clin Pharmacokinet | volume = 21 | issue = 1| pages = 11–26 | doi=10.2165/00003088-199121010-00002| pmid = 1717195 | s2cid = 35104089 }}</ref><ref>{{cite journal |vauthors=Van Hoogdalem EJ, de Boer AG, Breimer DD | year = 1991 | title = Pharmacokinetics of rectal drug administration, Part 2 | journal = Clin Pharmacokinet | volume = 21 | issue = 2| pages = 110–128 | doi=10.2165/00003088-199121020-00003 | pmid = 1884566| s2cid = 11720029 }}</ref><ref>{{cite journal |vauthors=Moolenaar F, Koning B, Huizinga T | year = 1979 | title = Biopharmaceutics of rectal administration of drugs in man. Absorption rate and bioavailability of phenobarbital and its sodium salt from rectal dosage forms | journal = [[International Journal of Pharmaceutics]] | volume = 4 | issue = 2| pages = 99–109 | doi=10.1016/0378-5173(79)90057-7}}</ref><ref>{{cite journal |vauthors=Graves NM, Holmes GB, Kriel RL, Jones-Saete C, Ong B, Ehresman DJ | year = 1989 | title = Relative bioavailability of rectally administered phenobarbital sodium parenteral solution | journal = DICP: The Annals of Pharmacotherapy | volume = 23 | issue = 7–8| pages = 565–568 | doi=10.1177/1060028089023007-806| pmid = 2763578 | s2cid = 27397387 }}</ref><ref>{{cite journal |vauthors=Moolenaar S, Bakker S, Visser J, Huizinga T | year = 1980 | title = Biopharmaceutics of rectal administration of drugs in man IX. Comparative biopharmaceutics of diazepam after single rectal, oral, intramuscular and intravenous administration in man | journal = International Journal of Pharmaceutics | volume = 5 | issue = 2| pages = 127–137 | doi=10.1016/0378-5173(80)90017-4}}</ref> The walls of the rectum absorb many medications quickly and effectively.<ref>[http://www.hpna.org.] {{webarchive|url=https://web.archive.org/web/20130126195447/http://www.hpna.org/|date=2013-01-26}} Nee, Douglas, Pharm D, MS. "Rectal Administration of Medications at the End of Life". HPNA Teleconference, December 6, 2006, accessed November 2013.</ref> Medications delivered to the distal one-third of the rectum at least partially avoid the "[[first pass effect]]" through the liver, which allows for greater [[bio-availability]] of many medications than that of the oral route. Rectal [[mucosa]] is highly [[vascularized]] tissue that allows for rapid and effective absorption of medications.<ref>{{cite web|url=http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_257.htm|title=Use of Rectal Meds for Palliative Care Patients. End of Life / Palliative Education Resource Center, Medical College of Wisconsin|website=mcw.edu|access-date=14 April 2018|url-status=dead|archive-url=https://web.archive.org/web/20140602060038/http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_257.htm|archive-date=2 June 2014}}</ref> A [[suppository]] is a solid [[dosage form]] that fits for [[rectal administration]]. In [[hospice care]], a specialized rectal [[Macy Catheter|catheter]], designed to provide comfortable and discreet administration of ongoing medications provides a practical way to deliver and retain liquid formulations in the [[distal]] rectum, giving health practitioners a way to leverage the established benefits of rectal administration. The [[Murphy drip]] is an example of rectal infusion.

====Parenteral route====
[[File:Needle-insertion-angles-1.png|thumb|Needle insertion angles for 4 types of parenteral administration of medication: intramuscular, subcutaneous, intravenous, and intradermal injection.]]
The parenteral route is any route that is not [[Enteral administration|enteral]] (''[[wikt:para-#Etymology 1|par-]]'' + ''enteral'').

Parenteral administration can be performed by [[Injection (medicine)|injection]], that is, using a needle (usually a [[hypodermic needle]]) and a [[syringe]],<ref>{{cite web|url=http://dictionary.cambridge.org/dictionary/english/injection|title=injection|website=Cambridge dictionary|access-date=2017-07-30|archive-url=https://web.archive.org/web/20170730202011/http://dictionary.cambridge.org/dictionary/english/injection|archive-date=2017-07-30|url-status=live}}</ref> or by the insertion of an [[indwelling catheter]].

Locations of application of parenteral administration include:
* Central nervous system:
:* [[Epidural]] (synonym: peridural) (injection or infusion into the [[epidural space]]), e.g. epidural anesthesia.
:* Intracerebral (into the cerebrum) administration by direct injection into the brain. Used in experimental research of chemicals<ref>{{cite web |url=http://www.neurotransmitter.net/mdmametabolites.html |title=MDMA (ecstasy) metabolites and neurotoxicity: No occurrence of MDMA neurotoxicity from metabolites when injected directly into brain, study shows |publisher=Neurotransmitter.net |access-date=2010-08-19 |archive-url=https://web.archive.org/web/20100807215102/http://www.neurotransmitter.net/mdmametabolites.html |archive-date=2010-08-07 |url-status=live }}</ref> and as a treatment for malignancies of the brain.<ref>{{cite journal|title=A potential application for the intracerebral injection of drugs entrapped within liposomes in the treatment of human cerebral gliomas  |date=2010-07-06 |pmc=1028604|last2=Firth|first2=G|last3=Oliver|first3=S|last4=Uttley|first4=D|last5=O'Laoire|first5=S|volume=48|issue=12|pages=1213–1219|journal=Journal of Neurology, Neurosurgery, and Psychiatry|doi=10.1136/jnnp.48.12.1213|pmid=2418156|author=McKeran RO, Firth G, Oliver S, Uttley D, O'Laoire S}}</ref> The intracerebral route can also interrupt the blood brain barrier from holding up against subsequent routes.<ref>{{cite journal|title=Blood–brain barrier changes following intracerebral injection of human recombinant tumor necrosis factor-α in the rat |doi=10.1007/BF01057957 |volume=20 |journal=Journal of Neuro-Oncology |pages=17–25 |year=1994 |author=Wright JL, Merchant RE|issue=1 |pmid=7807180 |s2cid=12445653 }}</ref>
:* [[intracerebroventricular injection|Intracerebroventricular]] (into the cerebral ventricles) administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable [[cancer pain]].<ref>{{cite journal |url=http://www.anesthesia-analgesia.org/cgi/content/full/89/5/1209 |title=Acute Decreases in Cerebrospinal Fluid Glutathione Levels after Intracerebroventricular Morphine for Cancer Pain |publisher=Anesthesia-analgesia.org |date=1999-06-22 |doi=10.1213/00000539-199911000-00023 |access-date=2010-08-19 |archive-url=https://web.archive.org/web/20060106043224/http://www.anesthesia-analgesia.org/cgi/content/full/89/5/1209 |archive-date=2006-01-06 |url-status=live |last1=Goudas |first1=Leonidas C. |last2=Langlade |first2=Agnes |last3=Serrie |first3=Alain |last4=Matson |first4=Wayne |last5=Milbury |first5=Paul |last6=Thurel |first6=Claude |last7=Sandouk |first7=Pierre |last8=Carr |first8=Daniel B. |journal=Anesthesia & Analgesia |volume=89 |issue=5 |pages=1209–1215 }}</ref>

[[File:Applying transdermal patch.jpg|thumb|A transdermal patch which delivers medication is applied to the skin. The patch is labelled with the time and date of administration as well as the administrator's initials.]]
[[File:Instilling nasal medication.jpg|thumb|A medical professional applies nose drops.]]
* Epicutaneous (application onto the skin). It can be used both for local effect as in allergy testing and typical [[local anesthesia]], as well as [[:wikt:systemic|systemic]] effects when the active substance diffuses through skin in a [[transdermal]] route.
*{{Anchor|buccal}}Sublingual and buccal medication administration is a way of giving someone medicine orally (by mouth). [[Sublingual administration]] is when medication is placed under the tongue to be absorbed by the body. The word "sublingual" means "under the tongue." Buccal administration involves placement of the drug between the gums and the cheek. These medications can come in the form of tablets, films, or sprays. Many drugs are designed for sublingual administration, including cardiovascular drugs, steroids, barbiturates, opioid analgesics with poor gastrointestinal bioavailability, enzymes and, increasingly, vitamins and minerals.
* [[Extra-amniotic administration]], between the [[endometrium]] and [[fetal membranes]].
* [[Nasal administration]] (through the nose) can be used for topically acting substances, as well as for [[Insufflation (medicine)|insufflation]] of e.g. [[decongestant]] nasal sprays to be taken up along the [[respiratory tract]]. Such substances are also called ''inhalational'', e.g. [[inhalational anesthetics]].
* Intra-arterial (into an [[artery]]), e.g. [[vasodilator]] drugs in the treatment of [[vasospasm]] and [[thrombolytic drug]]s for treatment of [[embolism]].
* Intra-[[joint|articular]], into a joint space. It is generally performed by [[joint injection]]. It is mainly used for symptomatic relief in [[osteoarthritis]].
* [[Intracardiac]] (into the heart), e.g. [[adrenaline]] during [[cardiopulmonary resuscitation]] (no longer commonly performed).
* [[Intracavernous injection]], an injection into the base of the [[penis]].
* [[Intradermal]], (into the skin itself) is used for [[Skin allergy test|skin testing]] some [[allergens]], and also for [[mantoux test]] for [[tuberculosis]].
* Intralesional (into a skin lesion), is used for local skin lesions, e.g. acne medication.
* [[Intramuscular injection|Intramuscular]] (into a [[muscle]]), e.g. many [[vaccine]]s, antibiotics, and long-term psychoactive agents. Recreationally the colloquial term 'muscling' is used.<ref name="Fenway Community Health">{{cite web|url=http://www.fenwayhealth.org/site/PageServer?pagename=CM_efc_effects |website=Fenway Community Health|title = Crystal Meth: The Effects |publisher=[[Fenway Health]] |url-status = dead|archive-url = https://web.archive.org/web/20101210183228/http://www.fenwayhealth.org/site/PageServer?pagename=CM_efc_effects|archive-date = 10 December 2010}}</ref>
[[File:Instilling eye medication.jpg|thumb|Topical ocular administration]]
* Intraocular, into the eye, e.g., some medications for [[glaucoma]] or [[eye neoplasm]]s.
* [[Intraosseous infusion]] (into the [[bone]] marrow) is, in effect, an indirect intravenous access because the bone marrow drains directly into the venous system. This route is occasionally used for drugs and fluids in emergency medicine and pediatrics when intravenous access is difficult.
* [[intraperitoneal injection|Intraperitoneal]], (infusion or injection into the [[peritoneum]]) e.g. [[peritoneal dialysis]].
* [[Intrathecal]] (into the spinal canal) is most commonly used for spinal [[anesthesia]] and [[chemotherapy]].
* Intrauterine.
* [[Intravaginal administration]], in the [[vagina]].
* [[intravenous therapy|Intravenous]] (into a [[vein]]), e.g. many drugs, [[Parenteral nutrition|total parenteral nutrition]].
* [[Intravesical drug delivery|Intravesical]] infusion is into the urinary bladder.
* [[Intravitreal]], through the eye.
* Subcutaneous (under the skin).<ref>{{cite book|last=Malenka|first=Eric J. Nestler, Steven E. Hyman, Robert C.|title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience|year=2009|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-148127-4|edition=2nd}}</ref> This generally takes the form of [[subcutaneous injection]], e.g. with [[insulin]]. [[Skin popping]] is a slang term that includes subcutaneous injection, and is usually used in association with [[recreational drugs]]. In addition to injection, it is also possible to slowly infuse fluids subcutaneously in the form of [[hypodermoclysis]].
* [[transdermal technology|Transdermal]] (diffusion through the intact skin for systemic rather than topical distribution), e.g. [[transdermal patch]]es such as [[fentanyl]] in pain therapy, [[nicotine]] patches for treatment of [[Substance use disorder|addiction]] and [[Glyceryl trinitrate (pharmacology)|nitroglycerine]] for treatment of [[angina pectoris]].
* [[Perivascular administration]] (perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery).<ref>{{cite journal | author = Mylonaki I, Allémann É, Saucy F, Haefliger J-A, Delie F, Jordan O | year = 2017 | title = Perivascular medical devices and drug delivery systems: Making the right choices | url = https://archive-ouverte.unige.ch/unige:92897 | journal = Biomaterials | volume = 128 | pages = 56–68 | doi = 10.1016/j.biomaterials.2017.02.028 | pmid = 28288349 | access-date = 2020-03-23 | archive-date = 2020-04-23 | archive-url = https://web.archive.org/web/20200423234047/https://archive-ouverte.unige.ch/unige:92897 | url-status = live }}</ref>
* Transmucosal (diffusion through a mucous membrane), e.g. [[Insufflation (medicine)|insufflation]] (snorting) of [[cocaine]], [[sublingual]], i.e. under the tongue, [[Sublabial route of administration|sublabial]], i.e. between the lips and [[gingiva]], and oral spray or vaginal suppository for  [[nitroglycerine]].

===Topical route===
{{Main|Topical drug delivery}}
The definition of the topical route of administration sometimes states that both the application location and the [[pharmacodynamic]] effect thereof is local.<ref name="mw-topical"/>

In other cases, ''topical'' is defined as applied to a localized area of the body or to the surface of a body part regardless of the location of the effect.<ref name=freedict-topical/><ref name=dict-topical/> By this definition, [[topical administration]] also includes [[transdermal]] application, where the substance is administered onto the skin but is [[absorption (skin)|absorbed]] into the body to attain [[systemic administration|systemic]] distribution.

If defined strictly as having local effect, the topical route of administration can also include [[enteral administration]] of medications that are poorly absorbable by the [[gastrointestinal tract]]. One such medication is the antibiotic [[vancomycin]], which cannot be absorbed in the gastrointestinal tract and is used orally only as a treatment for [[Clostridioides difficile colitis|''Clostridioides difficile'' colitis]].<ref name=AHFS2015>{{cite web|title=Vancocin|url=https://www.drugs.com/monograph/vancocin.html|publisher=The American Society of Health-System Pharmacists|access-date=Sep 4, 2015|archive-url=https://web.archive.org/web/20150906002445/http://www.drugs.com/monograph/vancocin.html|archive-date=September 6, 2015|url-status=live}}</ref>

== Choice of routes ==
The reason for choice of routes of drug administration are governing by various factors:

* Physical and chemical properties of the drug. The physical properties are solid, liquid and gas. The chemical properties are solubility, stability, pH, irritancy etc.
* Site of desired action: the action may be localised and approachable or generalised and not approachable.
* Rate of extent of absorption of the drug from different routes.
* Effect of digestive juices and the first pass metabolism of drugs.
* Condition of the patient.

In acute situations, in [[emergency medicine]] and [[intensive care medicine]], drugs are most often given intravenously. This is the most reliable route, as in acutely ill patients the absorption of substances from the tissues and from the digestive tract can often be unpredictable due to altered blood flow or bowel motility.

===Convenience===
Enteral routes are generally the most convenient for the patient, as no punctures or [[sterile technique|sterile]] procedures are necessary. Enteral medications are therefore often preferred in the treatment of chronic disease. However, some drugs can not be used enterally because their absorption in the digestive tract is low or unpredictable. Transdermal administration is a comfortable alternative; there are, however, only a few drug preparations that are suitable for transdermal administration.

===Desired target effect===
Identical drugs can produce different results depending on the route of administration. For example, some drugs are not significantly absorbed into the bloodstream from the gastrointestinal tract and their action after enteral administration is therefore different from that after parenteral administration. This can be illustrated by the action of [[naloxone]] (Narcan), an antagonist of [[opiate]]s such as [[morphine]]. Naloxone counteracts opiate action in the [[central nervous system]] when given intravenously and is therefore used in the treatment of opiate overdose. The same drug, when swallowed, acts exclusively on the bowels; it is here used to treat constipation under opiate pain therapy and does not affect the pain-reducing effect of the opiate.

===Oral===
The oral route is generally the most convenient and costs the least.<ref name="Nursing Times"/> However, some drugs can cause [[gastrointestinal tract]] irritation.<ref name=DDS>{{cite web |url= http://www.ct.gov/dds/lib/dds/edsupp/medadmin_recert_part_ii.pdf |title= DDS Medication Administration Recertification Manual |date= 2006 |work= DDS Recertification Review Manual |publisher= State of [[Connecticut Department of Developmental Services]] |access-date= April 2, 2013 |archive-url= https://web.archive.org/web/20130514074151/http://www.ct.gov/dds/lib/dds/edsupp/medadmin_recert_part_ii.pdf |archive-date= May 14, 2013 |url-status= live }}</ref> For drugs that come in [[delayed release (pharmacology)|delayed release]] or [[Time Release Capsule|time-release]] formulations, breaking the tablets or capsules can lead to more rapid delivery of the drug than intended.<ref name="Nursing Times"/> The oral route is limited to [[Formulation#Pharmacy|formulations]] containing [[small molecule]]s only while biopharmaceuticals (usually proteins) would be  digested in the stomach and thereby become ineffective. Biopharmaceuticals have to be given by injection or infusion. However, recent research found various ways to improve oral bioavailability of these drugs. In particular permeation enhancers,<ref>{{cite journal|last1= Yamamoto |first1=A|last2= Ukai |first2=H | last3= Morishita |first3=M| last4= Katsumi |first4=H | title= Approaches to improve intestinal and transmucosal absorption of peptide and protein drugs |journal= Adv Drug Deliv Rev |date=2020|volume=211|pages=107537 |doi=10.1016/j.pharmthera.2020.107537|pmid=32201316|s2cid=214618193}}</ref> [[ionic liquid]]s,<ref>{{Cite journal|last1=Banerjee|first1=Amrita|last2=Ibsen|first2=Kelly|last3=Brown|first3=Tyler|last4=Chen|first4=Renwei |last5=Agatemor|first5=Christian|last6=Mitragotri|first6=Samir|date=2018-06-20|title=Ionic liquids for oral insulin delivery|journal=Proceedings of the National Academy of Sciences|language=en|pages=7296–7301|doi=10.1073/pnas.1722338115|issn=0027-8424|pmid=29941553|pmc=6048483|volume=115|issue=28|bibcode=2018PNAS..115.7296B|doi-access=free}}</ref> lipid-based nanocarriers,<ref>{{cite journal|last1= Haddadzadegan |first1=S|last2= Dorkoosh |first2=F | last3=Bernkop-Schnürch|first3=A|title= Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers |journal= Adv Drug Deliv Rev |date=2022|volume=182|pages=114097 |doi=10.1016/j.addr.2021.114097|pmid=34999121|doi-access=free}}</ref> enzyme inhibitors and microneedles<ref>{{cite journal|last1= Maher |first1=S|last2= Brayden|first2=DJ | title= Approaches to improve intestinal and transmucosal absorption of peptide and protein drugs |journal= Pharmacol Ther |date=2021| volume=177|pages=113925| doi=10.1016/j.addr.2021.113925|pmid=34418495|doi-access=free}}</ref> have shown potential.

[[Oral administration]] is often denoted "PO" from "per os", the Latin for "by mouth".

The bioavailability of oral administration is affected by the amount of drug that is absorbed across the [[intestinal epithelium]] and [[first-pass metabolism]].<ref name="Hebert 2013 pp. 17–39">{{cite book | last=Hebert | first=Mary F. | title=Clinical Pharmacology During Pregnancy | chapter=Impact of Pregnancy on Maternal Pharmacokinetics of Medications | publisher=Elsevier | year=2013 | isbn=978-0-12-386007-1 | doi=10.1016/b978-0-12-386007-1.00003-9 | pages=17–39}}</ref>

===Oral mucosal===
The [[oral mucosa]] is the mucous membrane lining the inside of the [[mouth]].

====Buccal====
[[Buccal administration|Buccally administered]] medication is achieved by placing the drug between [[gums]] and the inner lining of the [[cheek]].<ref name="LE.JENNIFER 2020">{{cite web | author=LE.JENNIFER | title=Drug Absorption - Clinical Pharmacology | website=MSD Manual Professional Edition | date=2020-03-27 | url=https://www.msdmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-absorption | access-date=2020-03-28 | archive-url=https://web.archive.org/web/20191031171922/https://www.msdmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-absorption | archive-date=2019-10-31 | url-status=live }}</ref><ref name="Kaminsky Bostwick Guthrie 2015 pp. 808–817"/> In comparison with sublingual tissue, buccal tissue is less permeable resulting in slower [[Absorption (pharmacology)|absorption]].<ref name="Kaminsky Bostwick Guthrie 2015 pp. 808–817"/>

====Sublabial====
{{main|Sublabial administration}}

====Sublingual====
[[Sublingual administration]] is fulfilled by placing the drug between the tongue and the lower surface of the mouth.<ref name="Kaminsky Bostwick Guthrie 2015 pp. 808–817"/> The [[sublingual mucosa]] is highly permeable and thereby provides access to the underlying expansive network composed of capillaries, leading to rapid drug absorption.<ref name="Kaminsky Bostwick Guthrie 2015 pp. 808–817"/>

===Intranasal===
Drug administration via the nasal cavity yields rapid drug absorption and therapeutic effects.<ref name="Kaminsky Bostwick Guthrie 2015 pp. 808–817">{{cite journal | last1=Kaminsky | first1=Bonnie M. | last2=Bostwick | first2=Jolene R. | last3=Guthrie | first3=Sally K. | title=Alternate Routes of Administration of Antidepressant and Antipsychotic Medications | journal=The Annals of Pharmacotherapy | publisher=SAGE Publications | volume=49 | issue=7 | date=2015-04-23 | issn=1060-0280 | pmid=25907529 | doi=10.1177/1060028015583893 | pages=808–817| s2cid=39802797 }}</ref> This is because drug absorption through the nasal passages does not go through the gut before entering [[capillaries]] situated at [[tissue cell]]s and then systemic circulation and such absorption route allows transport of drugs into the [[central nervous system]] via the pathways of [[olfactory]] and [[trigeminal nerve]].<ref name="Kaminsky Bostwick Guthrie 2015 pp. 808–817"/>

Intranasal absorption features low lipophilicity, enzymatic degradation within the nasal cavity, large molecular size, and rapid mucociliary clearance from the nasal passages, which explains the low [[bioavailability|risk of systemic exposure of the administered drug absorbed]] via intranasal.<ref name="Kaminsky Bostwick Guthrie 2015 pp. 808–817"/>

[[File:Capillaries.jpg|thumbnail|upright=2|center|Involved subjects' positions.]]

===Local===
By delivering drugs almost directly to the site of action, the risk of systemic [[adverse effect|side effects]] is reduced.<ref name="Nursing Times"/>

Skin absorption (dermal absorption), for example, is to directly deliver drug to the skin and, hopefully, to the systemic circulation.<ref name="Rodrigues Oliveira 2016 pp. 155–167">{{cite book | last1=Rodrigues | first1=Francisca | last2=Oliveira | first2=Maria Beatriz P.P. | title=Concepts and Models for Drug Permeability Studies | chapter=Cell-based in vitro models for dermal permeability studies | publisher=Elsevier | year=2016 | isbn=978-0-08-100094-6 | doi=10.1016/b978-0-08-100094-6.00010-9 | pages=155–167}}</ref> However, skin irritation may result, and for some forms such as creams or lotions, the dosage is difficult to control.<ref name=DDS/> Upon contact with the skin, the drug penetrates into the dead [[stratum corneum]] and can afterwards reach the viable [[epidermis]], the [[dermis]], and the [[blood vessel]]s.<ref name="Rodrigues Oliveira 2016 pp. 155–167"/>

===Parenteral===
The term parenteral is from para-1 'beside' + Greek enteron 'intestine' + -al. This name is due to the fact that it encompasses a route of administration that is not intestinal. However, in common English the term has mostly been used to describe the four most well-known routes of injection.

[[File:Intravenous therapy 2007-SEP-13-Singapore.JPG|thumb|A peripheral IV placed on the hand.]]
[[File:Intradermal injection.jpg|thumb|A medical professional performs an intradermal (ID) injection.]]

The term injection encompasses [[intravenous]] (IV), [[intramuscular]] (IM), [[subcutaneous injection|subcutaneous]] (SC) and [[Intradermal injection|intradermal]] (ID) administration.<ref>{{cite web|url=http://www.ismp.org/Tools/errorproneabbreviations.pdf|title=List of Error-Prone Abbreviations|website=Institute For Safe Medication Practices|access-date=14 April 2018|archive-url=https://web.archive.org/web/20160222201424/https://www.ismp.org/tools/errorproneabbreviations.pdf|archive-date=22 February 2016|url-status=live}}</ref>

Parenteral administration generally acts more rapidly than topical or enteral administration, with onset of action often occurring in 15–30 seconds for IV, 10–20 minutes for IM and 15–30 minutes for SC.<ref>{{cite web |url=https://www.gov.mb.ca/health/ems/guidelines/docs/A2.08.03.pdf |title=Routes for Drug Administration |date=2003 |work=Emergency Treatment Guidelines Appendix |publisher=Manitoba Health |access-date=April 2, 2013 |archive-url=https://web.archive.org/web/20131001174406/http://www.gov.mb.ca/health/ems/guidelines/docs/A2.08.03.pdf |archive-date=October 1, 2013 |url-status=dead }}</ref> They also have essentially 100% [[bioavailability]] and can be used for drugs that are poorly absorbed or ineffective when they are given orally.<ref name="Nursing Times">{{cite web |url=https://www.nursingtimes.net/clinical-archive/medicine-management/the-administration-of-medicines-19-11-2007/ |title=The Administration of Medicines |date=2007 |work=Nursing Practice Clinical Zones: Prescribing |publisher=NursingTimes.net |access-date=April 2, 2013 |archive-url=https://web.archive.org/web/20200102152352/https://www.nursingtimes.net/clinical-archive/medicine-management/the-administration-of-medicines-19-11-2007/ |archive-date=January 2, 2020 |url-status=live }}</ref> Some medications, such as certain [[antipsychotic]]s, can be administered as [[depot injection|long-acting intramuscular injections]].<ref>Stahl SM, Stahl's Essential Psychopharmacology: Neuroscientific basis and practical applications, New York: Cambridge University Press, 2008</ref> Ongoing [[IV infusion]]s can be used to deliver continuous medication or [[IV fluid|fluids]].<ref>Smeltzer SC Bare BG, Textbook of Medical-Surgical Nursing, 9th ed, Philadelphia: Lippincott, 2000.</ref>

Disadvantages of injections include potential pain or discomfort for the patient and the requirement of trained staff using [[aseptic technique]]s for administration.<ref name="Nursing Times"/> However, in some cases, patients are taught to self-inject, such as SC injection of insulin in patients with [[insulin-dependent diabetes mellitus]]. As the drug is delivered to the site of action extremely rapidly with IV injection, there is a risk of [[drug overdose|overdose]] if the dose has been calculated incorrectly, and there is an increased risk of side effects if the drug is administered too rapidly.<ref name="Nursing Times"/>

===Respiratory tract===

====Mouth inhalation====
[[File:Administering inhaled medication.jpg|thumb|A dummy wears a nebulizer mask, used to administer inhaled medications.]]

[[File:illu quiz lung05.jpg|thumb|upright=0.8|{{ordered list |[[trachea]] (conducting zone)
|main [[bronchus]] (conducting zone)
|[[lobar bronchus]] (conducting zone)
| [[segmental bronchus]] (conducting zone)
| [[subsegmental bronchus]] (conducting zone)
| conducting [[bronchiole]] (conducting zone)
| [[terminal bronchiole]] (conducting zone)
| [[respiratory bronchiole]] (transitional respiratory zone)
| [[alveolar duct]] (transitional respiratory zone)
| [[alveolar sac]] (transitional respiratory zone)
| [[Pulmonary alveolus|alveolus]] (transitional respiratory zone)}}<ref name="Ali 2010 pp. 209–246">{{cite book | last=Ali | first=Mohammed | title=Handbook of Non-Invasive Drug Delivery Systems | chapter=Pulmonary Drug Delivery | publisher=Elsevier | year=2010 | isbn=978-0-8155-2025-2 | doi=10.1016/b978-0-8155-2025-2.10009-5 | pages=209–246}}</ref><ref name="archive.is 2020">{{cite web | title=Lungs - Anatomy of the Respiratory System | website=archive.is | date=2020-03-29 | url=https://www.brainkart.com/article/Lungs---Anatomy-of-the-Respiratory-System_21915/ | archive-url=https://archive.today/20200329053609/https://www.brainkart.com/article/Lungs---Anatomy-of-the-Respiratory-System_21915/ | url-status=dead | archive-date=2020-03-29 | access-date=2020-03-29}}</ref><ref name="GetBodySmart 2017">{{cite web | title=Major Zones & Divisions | website=GetBodySmart | date=2017-10-30 | url=https://www.getbodysmart.com/respiratory-system/respiratory-system-anatomy | access-date=2020-03-29}}</ref><ref>{{Cite web |url=https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-Conducting-Zone-770x550.png |title=Diagram for conducting zone |access-date=2020-03-29 |archive-date=2020-03-29 |archive-url=https://archive.today/20200329080819/https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-Conducting-Zone-770x550.png |url-status=live }}</ref><ref>{{Cite web |url=https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-Respiratory-Zone-770x550.png |title=Diagram for respiratory zone |access-date=2020-03-29 |archive-date=2020-03-29 |archive-url=https://archive.today/20200329081010/https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-Respiratory-Zone-770x550.png |url-status=live }}</ref><ref>{{Cite web |url=https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-Upper-tract-770x550.png |title=Diagram for upper respiratory tract |access-date=2020-03-29 |archive-date=2020-03-29 |archive-url=https://archive.today/20200329081203/https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-Upper-tract-770x550.png |url-status=live }}</ref><ref>{{Cite web |url=https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-lower-tract-770x550.png |title=Diagram for lower respiratory tract |access-date=2020-03-29 |archive-date=2020-03-29 |archive-url=https://archive.today/20200329081254/https://www.getbodysmart.com/wp-content/uploads/2017/09/Respiratory-lower-tract-770x550.png |url-status=live }}</ref><ref>{{Cite web |url=https://www.getbodysmart.com/wp-content/uploads/2017/10/Test-yourself-with-answers-shown-504x550.png |title=Diagram for majour zones of respiratory system |access-date=2020-03-29 |archive-date=2020-03-29 |archive-url=https://archive.today/20200329081401/https://www.getbodysmart.com/wp-content/uploads/2017/10/Test-yourself-with-answers-shown-504x550.png |url-status=live }}</ref>]]

Inhaled medications can be absorbed quickly and act both locally and systemically.<ref name=DDS/> Proper technique with [[inhaler]] devices is necessary to achieve the correct dose. Some medications can have an unpleasant taste or irritate the mouth.<ref name=DDS/>

In general, only 20–50% of the pulmonary-delivered dose rendered in powdery particles will be deposited in the lung upon mouth inhalation.<ref name="Tandel Florence Misra 2011 pp. 429–479">{{cite book | last1=Tandel | first1=Hemal | last2=Florence | first2=Kiruba | last3=Misra | first3=Ambikanandan | title=Challenges in Delivery of Therapeutic Genomics and Proteomics | chapter=Protein and Peptide Delivery through Respiratory Pathway | publisher=Elsevier | year=2011 | isbn=978-0-12-384964-9 | doi=10.1016/b978-0-12-384964-9.00009-8 | pages=429–479}}</ref> The remainder of 50-70% undeposited aerosolized particles are cleared out of lung as soon as [[exhalation]].<ref name="Tandel Florence Misra 2011 pp. 429–479"/>

An inhaled powdery particle that is >8 μm is structurally predisposed to depositing in the central and conducting airways ([[conducting zone]]) by inertial impaction.<ref name="Tandel Florence Misra 2011 pp. 429–479"/>

An inhaled powdery particle that is between 3 and 8 μm in diameter tend to largely deposit in the [[Transitional zone (lung)|transitional zone]]s of the lung by sedimentation.<ref name="Tandel Florence Misra 2011 pp. 429–479"/>

An inhaled powdery particle that is <3 μm in diameter is structurally predisposed to depositing primarily in the [[respiratory region]]s of the peripheral lung via diffusion.<ref name="Tandel Florence Misra 2011 pp. 429–479"/>

Particles that deposit in the upper and central airways are generally absorbed systemically to great extent because they are only partially removed by [[mucociliary]] clearance, which results in orally mediated absorption when the transported mucus is swallowed, and first pass metabolism or incomplete absorption through loss at the fecal route can sometimes reduce the bioavailability.<ref>{{Cite journal|title=Cilia and Mucociliary Clearance|first1=Ximena M.|last1=Bustamante-Marin|first2=Lawrence E.|last2=Ostrowski|date=April 18, 2017|journal=Cold Spring Harbor Perspectives in Biology|volume=9|issue=4|pages=a028241|doi=10.1101/cshperspect.a028241|pmid=27864314|pmc=5378048}}</ref> This should in no way suggest to clinicians or researchers that inhaled particles are not a greater threat than swallowed particles, it merely signifies that a combination of both methods may occur with some particles, no matter the size of or lipo/hydrophilicity of the different particle surfaces.<ref name="Tandel Florence Misra 2011 pp. 429–479"/>

{{further|PM 2.5|PM 10}}

====Nasal inhalation====
Inhalation by nose of a substance is almost identical to oral inhalation, except that some of the drug is absorbed intranasally instead of in the oral cavity before entering the airways. Both methods can result in varying levels of the substance to be deposited in their respective initial cavities, and the level of mucus in either of these cavities will reflect the amount of substance swallowed. The rate of inhalation will usually determine the amount of the substance which enters the lungs. Faster inhalation results in more rapid absorption because more substance finds the lungs. Substances in a form that resists absorption in the lung will likely resist absorption in the nasal passage, and the oral cavity, and are often even more resistant to absorption after they fail absorption in the former cavities and are swallowed.

==Research==
Neural drug delivery is the next step beyond the basic addition of [[growth factors]] to [[nerve guidance conduits]]. [[Drug delivery systems]] allow the rate of growth factor release to be regulated over time, which is critical for creating an environment more closely representative of in vivo development environments.<ref>Lavik, E. and R. Langer, Tissue engineering; current state and perspectives. Applied Microbiology Biotechnology, 2004. 65: p. 1–8</ref>

==See also==
* [[ADME]]
* [[Catheter]]
* [[Dosage form]]
* [[Drug injection]]
* [[Ear instillation]]
* [[Hypodermic needle]]
* [[Intravenous marijuana syndrome]]
* [[List of medical inhalants]]
* [[Nanomedicine]]
* [[Absorption (pharmacology)]]

==References==
{{Reflist|30em}}

==External links==
* [https://web.archive.org/web/20090907020041/http://www.drug-delivery-systems.org/ The 10th US-Japan Symposium on Drug Delivery Systems]
* [https://web.archive.org/web/20090710064902/http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/DataStandardsManualmonographs/ucm071667.htm FDA Center for Drug Evaluation and Research Data Standards Manual: Route of Administration.]
* [https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/DataStandardsManualmonographs/ucm071666.htm FDA Center for Drug Evaluation and Research Data Standards Manual: Dosage Form.]{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}
* [http://www.nutritioncare.org/ A.S.P.E.N. American Society for Parenteral and Enteral Nutrition]
* {{MeshName|Drug Administration Routes}}

{{Dosage forms|state=expanded}}

{{DEFAULTSORT:Route Of Administration}}
[[Category:Drugs]]
[[Category:Pharmacokinetics]]
[[Category:Routes of administration| ]]