Editing Sumatriptan (section)

=== Pharmacokinetics ===
Sumatriptan is administered in several forms: tablets, [[subcutaneous injection]], and nasal spray. Oral administration (as [[succinate]] salt) has low [[bioavailability]], partly due to [[presystemic metabolism]]—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A rapid-release tablet formulation with the same bioavailability but a high concentration can achieve therapeutic effects on average 10–15 minutes earlier than other oral formulations.<ref>{{Cite web |title=Sumatriptan |url=https://go.drugbank.com/drugs/DB00669 |access-date=2025-03-04 |website=go.drugbank.com |language=en}}</ref> When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time.{{Citation needed|date=March 2025}}

There is no simple, direct relationship between sumatriptan concentration (pharmacokinetics) per se in the blood and its anti-migraine effect (pharmacodynamics). This paradox has, to some extent, been resolved by comparing the rates of absorption of the various sumatriptan formulations, rather than the absolute amounts of drug that they deliver.<ref>{{cite journal |vauthors=Fox AW |date=February 2004 |title=Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation |journal=Headache |volume=44 |issue=2 |pages=142–147 |doi=10.1111/j.1526-4610.2004.04030.x |pmid=14756852 |s2cid=25587940}}</ref><ref>{{cite journal |vauthors=Freidank-Mueschenborn E, Fox AW |date=June 2005 |title=Resolution of concentration-response differences in onset of effect between subcutaneous and oral sumatriptan |journal=Headache |volume=45 |issue=6 |pages=632–637 |doi=10.1111/j.1526-4610.2005.05129a.x |pmid=15953294 |s2cid=20755695}}</ref>

==== Metabolism ====
Sumatriptan is metabolised primarily by [[Monoamine oxidase|monoamine oxidase A]] into indol-3-yl-acetaldehyde and then into corresponding carboxylic acid. It is further modified by [[Glucuronosyltransferase|UDP-glucuronosyltransferase]] into a conjugate with [[glucuronic acid]]. Other pathways are mediated by [[Cytochrome P450 (individual enzymes)|cytochrome P450 isoenzymes]], which give an [[Amine oxide|''N''-oxide]] derivative, and ''N''-desmethyl and ''N,N''-didesmethyl forms (the latter can be converted into the aldehyde by monoamine oxidase A). ''N''-desmethyl derivative can also undergo a reaction with [[Cysteine|<small>D</small>-cysteine]].<ref name="Pöstges_2023">{{cite journal | vauthors = Pöstges T, Lehr M | title = Metabolism of sumatriptan revisited | journal = Pharmacology Research & Perspectives | volume = 11 | issue = 1 | pages = e01051 | date = February 2023 | pmid = 36655303 | pmc = 9849828 | doi = 10.1002/prp2.1051 }}</ref>

These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged.<ref name="AHFS2019" />
[[File:Sumatriptan metabolism pathway.png|center|thumb|881x881px|Sumatriptan metabolic pathways (MAO-A – monoamine oxidase A, CYP - cytochrome P450 isoenzymes)<ref name="Pöstges_2023" />]]