Editing Valproate (section)

==Overdose and toxicity==
{| class="wikitable" align="right"
|+ Therapeutic range of valproic acid
|-
|'''Form'''
|'''Lower limit'''
|'''Upper limit'''
|'''Unit'''
|-
| rowspan=2| Total (including<br /> [[Plasma protein binding|protein bound]])
| 50<ref name=mass>{{cite web|url=http://emedicine.medscape.com/article/2090462-overview|title=Valproic Acid Level| vauthors = Suzanne B |date=11 December 2013|access-date=5 June 2015|publisher=[[Medscape]]|url-status=live|archive-url=https://web.archive.org/web/20150504030450/http://emedicine.medscape.com/article/2090462-overview|archive-date=4 May 2015}}</ref> || 125<ref name=mass/> || μg/mL or mg/L
|-
| 350<ref name=molar>{{cite web|url=https://www.cadth.ca/media/pdf/lab-tests/06_Free_Valproic_Acid_Assay_e.pdf|title=Free Valproic Acid Assay (Reference – 2013.03.006) Notice of Assessment|date=April 2014|publisher=Canadian Agency for Drugs and Technologies in Health (CADTH) with INESSS's permission|access-date=5 June 2015|url-status=dead|archive-url=https://web.archive.org/web/20160303232944/https://www.cadth.ca/media/pdf/lab-tests/06_Free_Valproic_Acid_Assay_e.pdf|archive-date=3 March 2016}}</ref> || 700<ref name=molar/> || μmol/L
|-
| rowspan=2| Free
| 6<ref name=mass/> || 22<ref name=mass/> || μg/mL or mg/L
|-
| 35<ref name=molar/> || 70<ref name=molar/> || μmol/L
|}

Excessive amounts of valproic acid can result in [[somnolence]], [[tremor]], [[stupor]], [[respiratory depression]], [[coma]], [[metabolic acidosis]], and death. In general, serum or plasma valproic acid concentrations are in a range of 20–100&nbsp;mg/L during controlled therapy, but may reach 150–1500&nbsp;mg/L following acute poisoning. Monitoring of the serum level is often accomplished using commercial immunoassay techniques, although some laboratories employ [[Chromatography|gas or liquid chromatography.]]<ref>{{cite journal | vauthors = Sztajnkrycer MD | title = Valproic acid toxicity: overview and management | journal = Journal of Toxicology. Clinical Toxicology | volume = 40 | issue = 6 | pages = 789–801 | year = 2002 | pmid = 12475192 | doi = 10.1081/CLT-120014645 | s2cid = 23031095 }}</ref>
In contrast to other [[antiepileptic drugs]], at present there is little favorable evidence for salivary therapeutic drug monitoring. Salivary levels of valproic acid correlate poorly with serum levels, partly due to valproate's weak acid property (p''K''a of 4.9).<ref>{{cite journal | vauthors = Patsalos PN, Berry DJ | title = Therapeutic drug monitoring of antiepileptic drugs by use of saliva | journal = Therapeutic Drug Monitoring | volume = 35 | issue = 1 | pages = 4–29 | date = February 2013 | pmid = 23288091 | doi = 10.1097/FTD.0b013e31827c11e7 | s2cid = 15338188 }}</ref>

In severe intoxication, [[hemoperfusion]] or [[hemofiltration]] can be an effective means of hastening elimination of the drug from the body.<ref>{{cite journal | vauthors = Thanacoody RH | title = Extracorporeal elimination in acute valproic acid poisoning | journal = Clinical Toxicology | volume = 47 | issue = 7 | pages = 609–616 | date = August 2009 | pmid = 19656009 | doi = 10.1080/15563650903167772 | s2cid = 13592043 }}</ref><ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1622–1626.</ref> Supportive therapy should be given to all patients experiencing an overdose and urine output should be monitored.<ref name="Depakote FDA label" /> Supplemental [[Carnitine|<small>L</small>-carnitine]] is indicated in patients having an acute overdose<ref name=pmid16277730>{{cite journal | vauthors = Lheureux PE, Penaloza A, Zahir S, Gris M | title = Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? | journal = Critical Care | volume = 9 | issue = 5 | pages = 431–440 | date = October 2005 | pmid = 16277730 | pmc = 1297603 | doi = 10.1186/cc3742 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mock CM, Schwetschenau KH | title = Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy | journal = American Journal of Health-System Pharmacy | volume = 69 | issue = 1 | pages = 35–39 | date = January 2012 | pmid = 22180549 | doi = 10.2146/ajhp110049 }}</ref> and also [[Preventive medicine|prophylactically]]<ref name=pmid16277730/> in high risk patients. [[Acetylcarnitine|Acetyl-<small>L</small>-carnitine]] lowers [[hyperammonemia]] less markedly<ref>{{cite journal | vauthors = Matsuoka M, Igisu H | title = Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia | journal = Biochemical Pharmacology | volume = 46 | issue = 1 | pages = 159–164 | date = July 1993 | pmid = 8347126 | doi = 10.1016/0006-2952(93)90360-9 }}</ref> than [[Carnitine|<small>L</small>-carnitine]]. <!-- It is important for people to know the comparison between L-carnitine and Acetyl-L-carnitine for VPA induced hyperammonemia. -->