Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects.
Identifieur interne : 001662 ( PubMed/Corpus ); précédent : 001661; suivant : 001663Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects.
Auteurs : H Christopher Hyson ; Karl Kieburtz ; Ira Shoulson ; Michael Mcdermott ; Bernard Ravina ; Elisabeth A. De Blieck ; Merit E. Cudkowicz ; Robert J. Ferrante ; Peter Como ; Sam Frank ; Carol Zimmerman ; Merit E. Cudkowicz ; Kimberly Ferrante ; Kristyn Newhall ; Danna Jennings ; Tammie Kelsey ; Francis Walker ; Vicki Hunt ; Susan Daigneault ; Michele Goldstein ; Joseph Weber ; Arthur Watts ; M Flint Beal ; Susan E. Browne ; Linda J. MetakisSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2010.
English descriptors
- KwdEn :
- Analysis of Variance, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Huntington Disease (drug therapy), Male, Treatment Outcome, Ubiquinone (administration & dosage), Ubiquinone (adverse effects), Ubiquinone (analogs & derivatives), Ubiquinone (therapeutic use).
- MESH :
- chemical , administration & dosage : Ubiquinone.
- chemical , adverse effects : Ubiquinone.
- chemical , analogs & derivatives : Ubiquinone.
- drug therapy : Huntington Disease.
- chemical , therapeutic use : Ubiquinone.
- Analysis of Variance, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Male, Treatment Outcome.
Abstract
Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 μg/mL (baseline, n = 28), 5.59 ± 2.24 μg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 μg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 μg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 μg/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.
DOI: 10.1002/mds.22408
PubMed: 20669312
Links to Exploration step
pubmed:20669312Le document en format XML
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De Blieck</name></author><author><name sortKey="Cudkowicz, Merit E" sort="Cudkowicz, Merit E" uniqKey="Cudkowicz M" first="Merit E" last="Cudkowicz">Merit E. Cudkowicz</name></author><author><name sortKey="Ferrante, Robert J" sort="Ferrante, Robert J" uniqKey="Ferrante R" first="Robert J" last="Ferrante">Robert J. Ferrante</name></author><author><name sortKey="Como, Peter" sort="Como, Peter" uniqKey="Como P" first="Peter" last="Como">Peter Como</name></author><author><name sortKey="Frank, Sam" sort="Frank, Sam" uniqKey="Frank S" first="Sam" last="Frank">Sam Frank</name></author><author><name sortKey="Zimmerman, Carol" sort="Zimmerman, Carol" uniqKey="Zimmerman C" first="Carol" last="Zimmerman">Carol Zimmerman</name></author><author><name sortKey="Cudkowicz, Merit E" sort="Cudkowicz, Merit E" uniqKey="Cudkowicz M" first="Merit E" last="Cudkowicz">Merit E. Cudkowicz</name></author><author><name sortKey="Ferrante, Kimberly" sort="Ferrante, Kimberly" uniqKey="Ferrante K" first="Kimberly" last="Ferrante">Kimberly Ferrante</name></author><author><name sortKey="Newhall, Kristyn" sort="Newhall, Kristyn" uniqKey="Newhall K" first="Kristyn" last="Newhall">Kristyn Newhall</name></author><author><name sortKey="Jennings, Danna" sort="Jennings, Danna" uniqKey="Jennings D" first="Danna" last="Jennings">Danna Jennings</name></author><author><name sortKey="Kelsey, Tammie" sort="Kelsey, Tammie" uniqKey="Kelsey T" first="Tammie" last="Kelsey">Tammie Kelsey</name></author><author><name sortKey="Walker, Francis" sort="Walker, Francis" uniqKey="Walker F" first="Francis" last="Walker">Francis Walker</name></author><author><name sortKey="Hunt, Vicki" sort="Hunt, Vicki" uniqKey="Hunt V" first="Vicki" last="Hunt">Vicki Hunt</name></author><author><name sortKey="Daigneault, Susan" sort="Daigneault, Susan" uniqKey="Daigneault S" first="Susan" last="Daigneault">Susan Daigneault</name></author><author><name sortKey="Goldstein, Michele" sort="Goldstein, Michele" uniqKey="Goldstein M" first="Michele" last="Goldstein">Michele Goldstein</name></author><author><name sortKey="Weber, Joseph" sort="Weber, Joseph" uniqKey="Weber J" first="Joseph" last="Weber">Joseph Weber</name></author><author><name sortKey="Watts, Arthur" sort="Watts, Arthur" uniqKey="Watts A" first="Arthur" last="Watts">Arthur Watts</name></author><author><name sortKey="Beal, M Flint" sort="Beal, M Flint" uniqKey="Beal M" first="M Flint" last="Beal">M Flint Beal</name></author><author><name sortKey="Browne, Susan E" sort="Browne, Susan E" uniqKey="Browne S" first="Susan E" last="Browne">Susan E. Browne</name></author><author><name sortKey="Metakis, Linda J" sort="Metakis, Linda J" uniqKey="Metakis L" first="Linda J" last="Metakis">Linda J. Metakis</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Analysis of Variance</term><term>Dose-Response Relationship, Drug</term><term>Drug Administration Schedule</term><term>Drug-Related Side Effects and Adverse Reactions</term><term>Female</term><term>Humans</term><term>Huntington Disease (drug therapy)</term><term>Male</term><term>Treatment Outcome</term><term>Ubiquinone (administration & dosage)</term><term>Ubiquinone (adverse effects)</term><term>Ubiquinone (analogs & derivatives)</term><term>Ubiquinone (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Ubiquinone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Ubiquinone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Ubiquinone</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Huntington Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Ubiquinone</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Analysis of Variance</term><term>Dose-Response Relationship, Drug</term><term>Drug Administration Schedule</term><term>Drug-Related Side Effects and Adverse Reactions</term><term>Female</term><term>Humans</term><term>Male</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 μg/mL (baseline, n = 28), 5.59 ± 2.24 μg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 μg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 μg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 μg/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">20669312</PMID><DateCreated><Year>2010</Year><Month>09</Month><Day>14</Day></DateCreated><DateCompleted><Year>2010</Year><Month>12</Month><Day>28</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>25</Volume><Issue>12</Issue><PubDate><Year>2010</Year><Month>Sep</Month><Day>15</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects.</ArticleTitle><Pagination><MedlinePgn>1924-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.22408</ELocationID><Abstract><AbstractText>Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 μg/mL (baseline, n = 28), 5.59 ± 2.24 μg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 μg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 μg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 μg/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.</AbstractText><CopyrightInformation>© 2010 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><CollectiveName>Huntington Study Group Pre2CARE Investigators</CollectiveName><AffiliationInfo><Affiliation>University of Western Ontario, London, ON, Canada. chyson@uwo.ca</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hyson</LastName><ForeName>H Christopher</ForeName><Initials>HC</Initials></Author><Author ValidYN="Y"><LastName>Kieburtz</LastName><ForeName>Karl</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Shoulson</LastName><ForeName>Ira</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>McDermott</LastName><ForeName>Michael</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Ravina</LastName><ForeName>Bernard</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>de Blieck</LastName><ForeName>Elisabeth A</ForeName><Initials>EA</Initials></Author><Author ValidYN="Y"><LastName>Cudkowicz</LastName><ForeName>Merit E</ForeName><Initials>ME</Initials></Author><Author ValidYN="Y"><LastName>Ferrante</LastName><ForeName>Robert J</ForeName><Initials>RJ</Initials></Author><Author ValidYN="Y"><LastName>Como</LastName><ForeName>Peter</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Frank</LastName><ForeName>Sam</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Zimmerman</LastName><ForeName>Carol</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Cudkowicz</LastName><ForeName>Merit E</ForeName><Initials>ME</Initials></Author><Author ValidYN="Y"><LastName>Ferrante</LastName><ForeName>Kimberly</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Newhall</LastName><ForeName>Kristyn</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Jennings</LastName><ForeName>Danna</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Kelsey</LastName><ForeName>Tammie</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Walker</LastName><ForeName>Francis</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Hunt</LastName><ForeName>Vicki</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Daigneault</LastName><ForeName>Susan</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Goldstein</LastName><ForeName>Michele</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Weber</LastName><ForeName>Joseph</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Watts</LastName><ForeName>Arthur</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Beal</LastName><ForeName>M Flint</ForeName><Initials>MF</Initials></Author><Author ValidYN="Y"><LastName>Browne</LastName><ForeName>Susan E</ForeName><Initials>SE</Initials></Author><Author ValidYN="Y"><LastName>Metakis</LastName><ForeName>Linda J</ForeName><Initials>LJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>1339-63-5</RegistryNumber><NameOfSubstance UI="D014451">Ubiquinone</NameOfSubstance></Chemical><Chemical><RegistryNumber>EJ27X76M46</RegistryNumber><NameOfSubstance UI="C024989">coenzyme Q10</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000704">Analysis of Variance</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004305">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004334">Drug Administration Schedule</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D064420">Drug-Related Side Effects and Adverse Reactions</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006816">Huntington Disease</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016896">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D014451">Ubiquinone</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000008">administration & dosage</QualifierName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000031">analogs & derivatives</QualifierName><QualifierName MajorTopicYN="N" UI="Q000627">therapeutic use</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>7</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>7</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>12</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId 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