Urinary excretion of valproate metabolites in children and adolescents

The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross‐sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carrie...

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Veröffentlicht in:Biopharmaceutics & drug disposition 2000-11, Vol.21 (8), p.327-330
Hauptverfasser: Reith, David M., Andrews, Jaymie, Parker-Scott, Suzie, Eadie, Mervyn J.
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container_issue 8
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container_title Biopharmaceutics & drug disposition
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creator Reith, David M.
Andrews, Jaymie
Parker-Scott, Suzie
Eadie, Mervyn J.
description The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross‐sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA‐glucuronide, 3‐oxo‐VPA and 4‐OH‐VPA were calculated by relating 24‐h recovery of these metabolites from urine to daily VPA dose. VPA, 3‐oxo‐VPA and 2‐en‐valproic acid (2‐en‐VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA‐glucuronide in children 10 years and younger was smaller than in older children (p
doi_str_mv 10.1002/bdd.247
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A cross‐sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA‐glucuronide, 3‐oxo‐VPA and 4‐OH‐VPA were calculated by relating 24‐h recovery of these metabolites from urine to daily VPA dose. VPA, 3‐oxo‐VPA and 2‐en‐valproic acid (2‐en‐VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA‐glucuronide in children 10 years and younger was smaller than in older children (p&lt;0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p&lt;0.01). LTG comedication had a stronger association with a higher proportion of dose being recovered as VPA‐glucuronide on multivariate analysis than did the age group (p=0.001 versus p&lt;0.05). In conclusion, older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA‐glucuronide. Copyright © 2000 John Wiley &amp; Sons, Ltd.</description><identifier>ISSN: 0142-2782</identifier><identifier>EISSN: 1099-081X</identifier><identifier>DOI: 10.1002/bdd.247</identifier><identifier>PMID: 11514952</identifier><identifier>CODEN: BDDID8</identifier><language>eng</language><publisher>Chichester, UK: John Wiley &amp; Sons, Ltd</publisher><subject>Adolescent ; Aging - metabolism ; Anticonvulsants - urine ; Anticonvulsants. Antiepileptics. 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Drug Dispos</addtitle><description>The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross‐sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA‐glucuronide, 3‐oxo‐VPA and 4‐OH‐VPA were calculated by relating 24‐h recovery of these metabolites from urine to daily VPA dose. VPA, 3‐oxo‐VPA and 2‐en‐valproic acid (2‐en‐VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA‐glucuronide in children 10 years and younger was smaller than in older children (p&lt;0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p&lt;0.01). LTG comedication had a stronger association with a higher proportion of dose being recovered as VPA‐glucuronide on multivariate analysis than did the age group (p=0.001 versus p&lt;0.05). In conclusion, older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA‐glucuronide. Copyright © 2000 John Wiley &amp; Sons, Ltd.</description><subject>Adolescent</subject><subject>Aging - metabolism</subject><subject>Anticonvulsants - urine</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromatography, Gas</subject><subject>Cross-Sectional Studies</subject><subject>Drug Combinations</subject><subject>Drug Interactions</subject><subject>Female</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Pharmacology. 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Antiepileptics. Antiparkinson agents</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromatography, Gas</topic><topic>Cross-Sectional Studies</topic><topic>Drug Combinations</topic><topic>Drug Interactions</topic><topic>Female</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Triazines - pharmacokinetics</topic><topic>Valproic Acid - urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reith, David M.</creatorcontrib><creatorcontrib>Andrews, Jaymie</creatorcontrib><creatorcontrib>Parker-Scott, Suzie</creatorcontrib><creatorcontrib>Eadie, Mervyn J.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Biopharmaceutics &amp; drug disposition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reith, David M.</au><au>Andrews, Jaymie</au><au>Parker-Scott, Suzie</au><au>Eadie, Mervyn J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Urinary excretion of valproate metabolites in children and adolescents</atitle><jtitle>Biopharmaceutics &amp; drug disposition</jtitle><addtitle>Biopharm. Drug Dispos</addtitle><date>2000-11</date><risdate>2000</risdate><volume>21</volume><issue>8</issue><spage>327</spage><epage>330</epage><pages>327-330</pages><issn>0142-2782</issn><eissn>1099-081X</eissn><coden>BDDID8</coden><abstract>The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross‐sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA‐glucuronide, 3‐oxo‐VPA and 4‐OH‐VPA were calculated by relating 24‐h recovery of these metabolites from urine to daily VPA dose. VPA, 3‐oxo‐VPA and 2‐en‐valproic acid (2‐en‐VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA‐glucuronide in children 10 years and younger was smaller than in older children (p&lt;0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p&lt;0.01). LTG comedication had a stronger association with a higher proportion of dose being recovered as VPA‐glucuronide on multivariate analysis than did the age group (p=0.001 versus p&lt;0.05). In conclusion, older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA‐glucuronide. Copyright © 2000 John Wiley &amp; Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley &amp; Sons, Ltd</pub><pmid>11514952</pmid><doi>10.1002/bdd.247</doi><tpages>4</tpages></addata></record>
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source Wiley Online Library - AutoHoldings Journals; MEDLINE
subjects Adolescent
Aging - metabolism
Anticonvulsants - urine
Anticonvulsants. Antiepileptics. Antiparkinson agents
Biological and medical sciences
Biotransformation
Child
Child, Preschool
Chromatography, Gas
Cross-Sectional Studies
Drug Combinations
Drug Interactions
Female
Humans
Hydrolysis
Male
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Triazines - pharmacokinetics
Valproic Acid - urine
title Urinary excretion of valproate metabolites in children and adolescents
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