Editing Haloperidol (section)

=== Pharmacokinetics ===
==== By mouth ====
The [[bioavailability]] of oral haloperidol ranges from 60 to 70%. However, there is a wide variance in reported mean [[Cmax (pharmacology)|T<sub>max</sub>]] and [[Biological half-life|T<sub>1/2</sub>]] in different studies, ranging from 1.7 to 6.1 hours and 14.5 to 36.7 hours respectively.<ref name=PK1999 >{{cite journal | vauthors = Kudo S, Ishizaki T | title = Pharmacokinetics of haloperidol: an update | journal = Clinical Pharmacokinetics | volume = 37 | issue = 6 | pages = 435–456 | date = December 1999 | pmid = 10628896 | doi = 10.2165/00003088-199937060-00001 | s2cid = 71360020 }}</ref>

==== Intramuscular injections ====
[[File:Haldol Decanoate.jpg|thumb|right|Haldol Decanoate for injection into muscle<ref name=EMC>{{cite web |title=Haldol Decanoate - Summary of Product Characteristics (SmPC) - (emc) |url=https://www.medicines.org.uk/emc/product/968/smpc |website=www.medicines.org.uk |access-date=26 December 2021}}</ref>]]

The drug is well and rapidly absorbed with a high bioavailability when injected intramuscularly. The T<sub>max</sub> is 20 minutes in healthy individuals and 33.8 minutes in patients with schizophrenia. The mean T<sub>1/2</sub> is 20.7 hours.<ref name="PK1999" /> The [[decanoate]] injectable formulation is for intramuscular administration only and is not intended to be used intravenously. The plasma concentrations of haloperidol decanoate reach a peak at about six days after the injection, falling thereafter, with an approximate half-life of three weeks.<ref>{{cite web |url = https://www.drugs.com/pro/haldol-decanoate.html |title = drugs.com |url-status = live |archive-url = https://web.archive.org/web/20110810064415/http://www.drugs.com/pro/haldol-decanoate.html |archive-date = 10 August 2011 }}</ref>

==== Intravenous injections ====
The bioavailability is 100% in intravenous (IV) injection, and the very rapid onset of action is seen within seconds. The T<sub>1/2</sub> is 14.1 to 26.2 hours. The apparent volume of distribution is between 9.5 and 21.7 L/kg.<ref name=PK1999 />  The duration of action is four to six hours.

==== Therapeutic concentrations ====
Plasma levels of five to 15 micrograms per liter are typically seen for therapeutic response (Ulrich S, et al. Clin Pharmacokinet. 1998). The determination of plasma levels is rarely used to calculate dose adjustments but can be useful to check compliance.

The concentration of haloperidol in brain tissue is about 20-fold higher compared to blood levels. It is slowly eliminated from brain tissue,<ref name="Kornhuber1999">{{cite journal | vauthors = Kornhuber J, Schultz A, Wiltfang J, Meineke I, Gleiter CH, Zöchling R, Boissl KW, Leblhuber F, Riederer P | title = Persistence of haloperidol in human brain tissue | journal = The American Journal of Psychiatry | volume = 156 | issue = 6 | pages = 885–890 | date = June 1999 | pmid = 10360127 | doi = 10.1176/ajp.156.6.885 }}</ref>  which may explain the slow disappearance of side effects when the medication is stopped.<ref name="Kornhuber1999" /><ref>{{cite journal | vauthors = Kornhuber J, Wiltfang J, Riederer P, Bleich S | title = Neuroleptic drugs in the human brain: clinical impact of persistence and region-specific distribution | journal = European Archives of Psychiatry and Clinical Neuroscience | volume = 256 | issue = 5 | pages = 274–280 | date = August 2006 | pmid = 16788768 | doi = 10.1007/s00406-006-0661-7 | s2cid = 9565741 }}</ref>

==== Distribution and metabolism ====
Haloperidol is heavily protein bound in human plasma, with a free fraction of only 7.5 to 11.6%. It is also extensively metabolized in the liver with only about 1% of the administered dose excreted unchanged in the urine. The greatest proportion of the hepatic clearance is by [[glucuronidation]], followed by reduction and CYP-mediated oxidation, primarily by [[CYP3A4]].<ref name=PK1999 /> Haloperidol is metabolized into [[HPP+|HPP<sup>+</sup>]], a [[monoaminergic neurotoxin]] related to [[MPTP]], by CYP3A enzymes.<ref name="Kostrzewa2022">{{cite book | vauthors = Kostrzewa RM | title=Handbook of Neurotoxicity | chapter=Survey of Selective Monoaminergic Neurotoxins Targeting Dopaminergic, Noradrenergic, and Serotoninergic Neurons | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-031-15079-1 | doi=10.1007/978-3-031-15080-7_53 | pages=159–198}}</ref><ref name="Igarashi1998">{{cite journal | vauthors = Igarashi K | title=The Possible Role of an Active Metafbollte Derived from the Neuroleptic Agent Haloperidol in Drug-Induced Parkinsonism | journal=Journal of Toxicology: Toxin Reviews | volume=17 | issue=1 | date=1998 | issn=0731-3837 | doi=10.3109/15569549809006488 | pages=27–38}}</ref><ref name="GórskaMarszałłSloderbach2015">{{cite journal | vauthors = Górska A, Marszałł M, Sloderbach A | title = Neurotoksyczność pirydyniowych metabolitów haloperydolu | trans-title = The neurotoxicity of pyridinium metabolites of haloperidol | language = Polish | journal = Postepy Hig Med Dosw (Online) | volume = 69 | issue = | pages = 1169–1175 | date = October 2015 | pmid = 26561842 | doi = 10.5604/17322693.1175009 | doi-broken-date = 1 November 2024 | url = | doi-access = free }}</ref>