Editing Azapirone (section)

=== Pharmacokinetics ===

Azapirones are poorly but nonetheless appreciably [[absorption (pharmacokinetics)|absorbed]] and have a rapid [[onset of action]], but have only very short [[half-life|half-live]]s ranging from 1–3 hours. As a result, they must be administered 2&ndash;3 times a day. The only exception to this rule is umespirone, which has a very long duration with a single dose lasting as long as 23 hours.<ref name="pmid7957544">{{cite journal |vauthors=Holland RL, Wesnes K, Dietrich B | title = Single dose human pharmacology of umespirone | journal = European Journal of Clinical Pharmacology | volume = 46 | issue = 5 | pages = 461–8 | year = 1994 | pmid = 7957544 | doi = 10.1007/bf00191912| s2cid = 12117650 }}</ref> Unfortunately, umespirone has not been commercialized. Although never commercially produced, Bristol-Myers Squibb applied for a patent on October 28, 1993, and received the patent on July 11, 1995, for an extended release formulation of buspirone.<ref>{{ cite patent | country = US | number = 5431922 | status = patent | title = Method for administration of buspirone | gdate = 1995-07-11 | fdate =  1993-10-23 | inventor = Nicklasson AGM | assign1 = Bristol-Myers Squibb Company url=https://patents.google.com/patent/US5431922 }}</ref> An [[Time Release Technology (medicine)|extended release]] formulation of gepirone is currently under development and if approved, should help to improve this issue.

[[Metabolism]] of azapirones occurs in the [[liver]] and they are [[excretion|excreted]] in [[urine]] and [[feces]]. A common [[metabolite]] of several azapirones including [[buspirone]], [[gepirone]], [[ipsapirone]], [[revospirone]], and [[tandospirone]] is [[1-(2-pyrimidinyl)piperazine]] (1-PP).<ref name="pmid8750726">{{cite journal |vauthors=Manahan-Vaughan D, Anwyl R, Rowan MJ | title = The azapirone metabolite 1-(2-pyrimidinyl)piperazine depresses excitatory synaptic transmission in the hippocampus of the alert rat via 5-HT1A receptors | journal = European Journal of Pharmacology | volume = 294 | issue = 2–3 | pages = 617–24 |date=December 1995 | pmid = 8750726 | doi = 10.1016/0014-2999(95)00605-2}}</ref><ref name="pmid1681447">{{cite journal |vauthors=Blier P, Curet O, Chaput Y, de Montigny C | title = Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--II. Effects of acute administration of 1-PP and long-term administration of tandospirone on noradrenergic neurotransmission | journal = Neuropharmacology | volume = 30 | issue = 7 | pages = 691–701 |date=July 1991 | pmid = 1681447 | doi = 10.1016/0028-3908(91)90176-C| s2cid = 44297577 }}</ref><ref name="pmid2149168">{{cite journal |vauthors=Löscher W, Witte U, Fredow G, Traber J, Glaser T | title = The behavioural responses to 8-OH-DPAT, ipsapirone and the novel 5-HT1A receptor agonist Bay Vq 7813 in the pig | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 342 | issue = 3 | pages = 271–7 |date=September 1990 | pmid = 2149168 | doi = 10.1007/bf00169437| s2cid = 24769939 }}</ref> 1-PP possesses 5-HT<sub>1A</sub> partial agonist and α<sub>2</sub>-adrenergic antagonist actions and likely contributes overall mostly to side effects.<ref name="pmid8750726"/><ref name="pmid1681447"/><ref name="pmid12438536">{{cite journal |vauthors=Zuideveld KP, Rusiç-Pavletiç J, Maas HJ, Peletier LA, Van der Graaf PH, Danhof M | title = Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 303 | issue = 3 | pages = 1130–7 |date=December 2002 | pmid = 12438536 | doi = 10.1124/jpet.102.036798 | s2cid = 14139919 }}</ref>