Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy
Background and Objectives Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study wa...
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| Veröffentlicht in: | Clinical pharmacokinetics 2020-08, Vol.59 (8), p.1005-1012 |
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| creator | Wang, George Sam Bourne, David W. A. Klawitter, Jost Sempio, Cristina Chapman, Kevin Knupp, Kelly Wempe, Michael F. Borgelt, Laura Christians, Uwe Leonard, Jan Heard, Kennon Bajaj, Lalit |
| description | Background and Objectives
Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.
Methods
We conducted a prospective observational study evaluating the disposition of oral cannabidiol in children ( |
| doi_str_mv | 10.1007/s40262-020-00869-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_webof</sourceid><recordid>TN_cdi_webofscience_primary_000516184400001</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2433399001</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-fc3f8e489b9c18b1a5475aa9fb5343d4241bc36130cfb50c9e5013ecbacf67733</originalsourceid><addsrcrecordid>eNqNkMlKBDEQhoMoOo6-gAdp8CjRytJLjtKOCwiK6DmkM2kn0iZt0sOoT2-0XW7iqULx_VWVD6E9AkcEoDyOHGhBMVDAAFUh8NsamhBSCkwELdbRBBihOBcF20LbMT5CoijAJtpiFHiVwAm6ObWx99EO1rvMt9l1UF1WK-dUY-fWd_jW6sV3I2azlyEoPcTMuqxe2G4ejMtWdlhks952po-vO2ijVV00u191iu7PZnf1Bb66Pr-sT66wZmU-4FaztjK8Eo3QpGqIynmZKyXaJmeczTnlpNGsIAx0aoEWJgfCjG6UbouyZGyKDsa5ffDPSxMH-eiXwaWVknLGmBCQAlNER0oHH2MwreyDfVLhVRKQHxLlKFEmifJTonxLof2v0cvmycx_It_WElCNwMo0vo3aGqfND5Y056QgFefpBaS2g_qwW_ulG1L08P_RRLORjolwDyb8fvKP-98B6dmdqA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2433399001</pqid></control><display><type>article</type><title>Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy</title><source>SpringerNature Journals</source><source>Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><creator>Wang, George Sam ; Bourne, David W. A. ; Klawitter, Jost ; Sempio, Cristina ; Chapman, Kevin ; Knupp, Kelly ; Wempe, Michael F. ; Borgelt, Laura ; Christians, Uwe ; Leonard, Jan ; Heard, Kennon ; Bajaj, Lalit</creator><creatorcontrib>Wang, George Sam ; Bourne, David W. A. ; Klawitter, Jost ; Sempio, Cristina ; Chapman, Kevin ; Knupp, Kelly ; Wempe, Michael F. ; Borgelt, Laura ; Christians, Uwe ; Leonard, Jan ; Heard, Kennon ; Bajaj, Lalit</creatorcontrib><description>Background and Objectives
Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.
Methods
We conducted a prospective observational study evaluating the disposition of oral cannabidiol in children (< 18 years of age) receiving cannabidiol extracts for epilepsy. Subjects underwent serial blood draws after oral cannabidiol administration. Cannabidiol and metabolites, along with anticonvulsant concentrations were determined.
Results
Twenty-nine patients had sufficient pharmacokinetic data and were included in the analysis. Mean age was 9.7 years (standard deviation 4.3) and 17 patients (59%) were male. Median peak plasma cannabidiol concentrations was 13.1 ng/mL (interquartile range 6.8–39.3 ng mL); median time to peak of 2.0 h (interquartile range 2.0–4.0 h). Mean acute elimination half-life of oral cannabidiol was 6.2 h (standard deviation 1.8 h). There was an observed half-life of degradation of 533 days noted for cannabidiol concentrations when stored for 0.6–3.1 years. There was some impact on cannabidiol pharmacokinetic parameters when cannabidiol was co-administered with zonisamide (elimination rate constant and V1) and levetiracetam (elimination rate constant).
Conclusions
In pediatric patients using oral cannabidiol-rich cannabis extract for epilepsy, the time to peak concentration of plasma cannabidiol and average acute elimination half-life were shorter than those reported for adults. Co-administration of zonisamide and levetiracetam had some impact on cannabidiol pharmacokinetic parameters. There was an observed degradation of plasma cannabidiol in long-term storage.
Clinical registration
ClinicalTrials.gov Identifer no. NCT02447198.</description><identifier>ISSN: 0312-5963</identifier><identifier>EISSN: 1179-1926</identifier><identifier>DOI: 10.1007/s40262-020-00869-z</identifier><identifier>PMID: 32048179</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Anticonvulsants ; Cannabidiol ; Convulsions & seizures ; Drug dosages ; Drug interactions ; Epilepsy ; FDA approval ; Internal Medicine ; Life Sciences & Biomedicine ; Medical marijuana ; Medicine ; Medicine & Public Health ; Metabolites ; Original Research Article ; Pain ; Pediatrics ; Pharmacokinetics ; Pharmacology & Pharmacy ; Pharmacology/Toxicology ; Pharmacotherapy ; Plasma ; Public health ; Science & Technology</subject><ispartof>Clinical pharmacokinetics, 2020-08, Vol.59 (8), p.1005-1012</ispartof><rights>Springer Nature Switzerland AG 2020</rights><rights>Copyright Springer Nature B.V. Aug 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>12</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000516184400001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c375t-fc3f8e489b9c18b1a5475aa9fb5343d4241bc36130cfb50c9e5013ecbacf67733</citedby><cites>FETCH-LOGICAL-c375t-fc3f8e489b9c18b1a5475aa9fb5343d4241bc36130cfb50c9e5013ecbacf67733</cites><orcidid>0000-0002-8095-612X ; 0000-0002-3005-1533</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40262-020-00869-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40262-020-00869-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,28253,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32048179$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, George Sam</creatorcontrib><creatorcontrib>Bourne, David W. A.</creatorcontrib><creatorcontrib>Klawitter, Jost</creatorcontrib><creatorcontrib>Sempio, Cristina</creatorcontrib><creatorcontrib>Chapman, Kevin</creatorcontrib><creatorcontrib>Knupp, Kelly</creatorcontrib><creatorcontrib>Wempe, Michael F.</creatorcontrib><creatorcontrib>Borgelt, Laura</creatorcontrib><creatorcontrib>Christians, Uwe</creatorcontrib><creatorcontrib>Leonard, Jan</creatorcontrib><creatorcontrib>Heard, Kennon</creatorcontrib><creatorcontrib>Bajaj, Lalit</creatorcontrib><title>Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy</title><title>Clinical pharmacokinetics</title><addtitle>Clin Pharmacokinet</addtitle><addtitle>CLIN PHARMACOKINET</addtitle><addtitle>Clin Pharmacokinet</addtitle><description>Background and Objectives
Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.
Methods
We conducted a prospective observational study evaluating the disposition of oral cannabidiol in children (< 18 years of age) receiving cannabidiol extracts for epilepsy. Subjects underwent serial blood draws after oral cannabidiol administration. Cannabidiol and metabolites, along with anticonvulsant concentrations were determined.
Results
Twenty-nine patients had sufficient pharmacokinetic data and were included in the analysis. Mean age was 9.7 years (standard deviation 4.3) and 17 patients (59%) were male. Median peak plasma cannabidiol concentrations was 13.1 ng/mL (interquartile range 6.8–39.3 ng mL); median time to peak of 2.0 h (interquartile range 2.0–4.0 h). Mean acute elimination half-life of oral cannabidiol was 6.2 h (standard deviation 1.8 h). There was an observed half-life of degradation of 533 days noted for cannabidiol concentrations when stored for 0.6–3.1 years. There was some impact on cannabidiol pharmacokinetic parameters when cannabidiol was co-administered with zonisamide (elimination rate constant and V1) and levetiracetam (elimination rate constant).
Conclusions
In pediatric patients using oral cannabidiol-rich cannabis extract for epilepsy, the time to peak concentration of plasma cannabidiol and average acute elimination half-life were shorter than those reported for adults. Co-administration of zonisamide and levetiracetam had some impact on cannabidiol pharmacokinetic parameters. There was an observed degradation of plasma cannabidiol in long-term storage.
Clinical registration
ClinicalTrials.gov Identifer no. NCT02447198.</description><subject>Anticonvulsants</subject><subject>Cannabidiol</subject><subject>Convulsions & seizures</subject><subject>Drug dosages</subject><subject>Drug interactions</subject><subject>Epilepsy</subject><subject>FDA approval</subject><subject>Internal Medicine</subject><subject>Life Sciences & Biomedicine</subject><subject>Medical marijuana</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolites</subject><subject>Original Research Article</subject><subject>Pain</subject><subject>Pediatrics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology & Pharmacy</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Plasma</subject><subject>Public health</subject><subject>Science & Technology</subject><issn>0312-5963</issn><issn>1179-1926</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkMlKBDEQhoMoOo6-gAdp8CjRytJLjtKOCwiK6DmkM2kn0iZt0sOoT2-0XW7iqULx_VWVD6E9AkcEoDyOHGhBMVDAAFUh8NsamhBSCkwELdbRBBihOBcF20LbMT5CoijAJtpiFHiVwAm6ObWx99EO1rvMt9l1UF1WK-dUY-fWd_jW6sV3I2azlyEoPcTMuqxe2G4ejMtWdlhks952po-vO2ijVV00u191iu7PZnf1Bb66Pr-sT66wZmU-4FaztjK8Eo3QpGqIynmZKyXaJmeczTnlpNGsIAx0aoEWJgfCjG6UbouyZGyKDsa5ffDPSxMH-eiXwaWVknLGmBCQAlNER0oHH2MwreyDfVLhVRKQHxLlKFEmifJTonxLof2v0cvmycx_It_WElCNwMo0vo3aGqfND5Y056QgFefpBaS2g_qwW_ulG1L08P_RRLORjolwDyb8fvKP-98B6dmdqA</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Wang, George Sam</creator><creator>Bourne, David W. A.</creator><creator>Klawitter, Jost</creator><creator>Sempio, Cristina</creator><creator>Chapman, Kevin</creator><creator>Knupp, Kelly</creator><creator>Wempe, Michael F.</creator><creator>Borgelt, Laura</creator><creator>Christians, Uwe</creator><creator>Leonard, Jan</creator><creator>Heard, Kennon</creator><creator>Bajaj, Lalit</creator><general>Springer International Publishing</general><general>Springer Nature</general><general>Springer Nature B.V</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><orcidid>https://orcid.org/0000-0002-8095-612X</orcidid><orcidid>https://orcid.org/0000-0002-3005-1533</orcidid></search><sort><creationdate>20200801</creationdate><title>Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy</title><author>Wang, George Sam ; Bourne, David W. A. ; Klawitter, Jost ; Sempio, Cristina ; Chapman, Kevin ; Knupp, Kelly ; Wempe, Michael F. ; Borgelt, Laura ; Christians, Uwe ; Leonard, Jan ; Heard, Kennon ; Bajaj, Lalit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-fc3f8e489b9c18b1a5475aa9fb5343d4241bc36130cfb50c9e5013ecbacf67733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anticonvulsants</topic><topic>Cannabidiol</topic><topic>Convulsions & seizures</topic><topic>Drug dosages</topic><topic>Drug interactions</topic><topic>Epilepsy</topic><topic>FDA approval</topic><topic>Internal Medicine</topic><topic>Life Sciences & Biomedicine</topic><topic>Medical marijuana</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolites</topic><topic>Original Research Article</topic><topic>Pain</topic><topic>Pediatrics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology & Pharmacy</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Plasma</topic><topic>Public health</topic><topic>Science & Technology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, George Sam</creatorcontrib><creatorcontrib>Bourne, David W. A.</creatorcontrib><creatorcontrib>Klawitter, Jost</creatorcontrib><creatorcontrib>Sempio, Cristina</creatorcontrib><creatorcontrib>Chapman, Kevin</creatorcontrib><creatorcontrib>Knupp, Kelly</creatorcontrib><creatorcontrib>Wempe, Michael F.</creatorcontrib><creatorcontrib>Borgelt, Laura</creatorcontrib><creatorcontrib>Christians, Uwe</creatorcontrib><creatorcontrib>Leonard, Jan</creatorcontrib><creatorcontrib>Heard, Kennon</creatorcontrib><creatorcontrib>Bajaj, Lalit</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Proquest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Clinical pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, George Sam</au><au>Bourne, David W. A.</au><au>Klawitter, Jost</au><au>Sempio, Cristina</au><au>Chapman, Kevin</au><au>Knupp, Kelly</au><au>Wempe, Michael F.</au><au>Borgelt, Laura</au><au>Christians, Uwe</au><au>Leonard, Jan</au><au>Heard, Kennon</au><au>Bajaj, Lalit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy</atitle><jtitle>Clinical pharmacokinetics</jtitle><stitle>Clin Pharmacokinet</stitle><stitle>CLIN PHARMACOKINET</stitle><addtitle>Clin Pharmacokinet</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>59</volume><issue>8</issue><spage>1005</spage><epage>1012</epage><pages>1005-1012</pages><issn>0312-5963</issn><eissn>1179-1926</eissn><abstract>Background and Objectives
Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.
Methods
We conducted a prospective observational study evaluating the disposition of oral cannabidiol in children (< 18 years of age) receiving cannabidiol extracts for epilepsy. Subjects underwent serial blood draws after oral cannabidiol administration. Cannabidiol and metabolites, along with anticonvulsant concentrations were determined.
Results
Twenty-nine patients had sufficient pharmacokinetic data and were included in the analysis. Mean age was 9.7 years (standard deviation 4.3) and 17 patients (59%) were male. Median peak plasma cannabidiol concentrations was 13.1 ng/mL (interquartile range 6.8–39.3 ng mL); median time to peak of 2.0 h (interquartile range 2.0–4.0 h). Mean acute elimination half-life of oral cannabidiol was 6.2 h (standard deviation 1.8 h). There was an observed half-life of degradation of 533 days noted for cannabidiol concentrations when stored for 0.6–3.1 years. There was some impact on cannabidiol pharmacokinetic parameters when cannabidiol was co-administered with zonisamide (elimination rate constant and V1) and levetiracetam (elimination rate constant).
Conclusions
In pediatric patients using oral cannabidiol-rich cannabis extract for epilepsy, the time to peak concentration of plasma cannabidiol and average acute elimination half-life were shorter than those reported for adults. Co-administration of zonisamide and levetiracetam had some impact on cannabidiol pharmacokinetic parameters. There was an observed degradation of plasma cannabidiol in long-term storage.
Clinical registration
ClinicalTrials.gov Identifer no. NCT02447198.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>32048179</pmid><doi>10.1007/s40262-020-00869-z</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-8095-612X</orcidid><orcidid>https://orcid.org/0000-0002-3005-1533</orcidid></addata></record> |
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| subjects | Anticonvulsants Cannabidiol Convulsions & seizures Drug dosages Drug interactions Epilepsy FDA approval Internal Medicine Life Sciences & Biomedicine Medical marijuana Medicine Medicine & Public Health Metabolites Original Research Article Pain Pediatrics Pharmacokinetics Pharmacology & Pharmacy Pharmacology/Toxicology Pharmacotherapy Plasma Public health Science & Technology |
| title | Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy |
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