{"id":"https://openalex.org/W4311933743","doi":"https://doi.org/10.1002/cpdd.1205","title":"Pharmacokinetic and Pharmacologic Characterization of the Dihydrotetrabenazine Isomers of Deutetrabenazine and Valbenazine","display_name":"Pharmacokinetic and Pharmacologic Characterization of the Dihydrotetrabenazine Isomers of Deutetrabenazine and Valbenazine","publication_year":2022,"publication_date":"2022-12-18","ids":{"openalex":"https://openalex.org/W4311933743","doi":"https://doi.org/10.1002/cpdd.1205","pmid":"https://pubmed.ncbi.nlm.nih.gov/36530055"},"language":"en","primary_location":{"id":"doi:10.1002/cpdd.1205","doi":"https://doi.org/10.1002/cpdd.1205","is_oa":true,"landing_page_url":"https://doi.org/10.1002/cpdd.1205","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cpdd.1205","source":{"id":"https://openalex.org/S2764863641","display_name":"Clinical Pharmacology in Drug Development","issn_l":"2160-763X","issn":["2160-763X","2160-7648"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","jufo-1","ki-jl-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Clinical Pharmacology in Drug Development","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cpdd.1205","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5038729165","display_name":"Satjit Brar","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I67391869","display_name":"Neurocrine Biosciences (United States)","ror":"https://ror.org/05d84mm26","country_code":"US","type":"company","lineage":["https://openalex.org/I67391869"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Satjit Brar","raw_affiliation_strings":["Neurocrine Biosciences, Inc., San Diego, California, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neurocrine Biosciences, Inc., San Diego, California, USA","institution_ids":["https://openalex.org/I67391869"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029621320","display_name":"Arjun Vijan","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210101297","display_name":"Jazz Pharmaceuticals (United States)","ror":"https://ror.org/019rsbe67","country_code":"US","type":"company","lineage":["https://openalex.org/I4210101297","https://openalex.org/I4210152300"]},{"id":"https://openalex.org/I67391869","display_name":"Neurocrine Biosciences (United States)","ror":"https://ror.org/05d84mm26","country_code":"US","type":"company","lineage":["https://openalex.org/I67391869"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Arjun Vijan","raw_affiliation_strings":["Neurocrine Biosciences, Inc., San Diego, California, USA","Current affiliation: Jazz Pharmaceuticals, Palo Alto, California, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neurocrine Biosciences, Inc., San Diego, California, USA","institution_ids":["https://openalex.org/I67391869"]},{"raw_affiliation_string":"Current affiliation: Jazz Pharmaceuticals, Palo Alto, California, USA","institution_ids":["https://openalex.org/I4210101297"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056608200","display_name":"Fiona L. Scott","orcid":"https://orcid.org/0000-0002-2461-4213","observed_orcids":["https://orcid.org/0000-0002-2461-4213"]},"institutions":[{"id":"https://openalex.org/I67391869","display_name":"Neurocrine Biosciences (United States)","ror":"https://ror.org/05d84mm26","country_code":"US","type":"company","lineage":["https://openalex.org/I67391869"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Fiona L. Scott","raw_affiliation_strings":["Neurocrine Biosciences, Inc., San Diego, California, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neurocrine Biosciences, Inc., San Diego, California, USA","institution_ids":["https://openalex.org/I67391869"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108884150","display_name":"Roland Jimenez","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I67391869","display_name":"Neurocrine Biosciences (United States)","ror":"https://ror.org/05d84mm26","country_code":"US","type":"company","lineage":["https://openalex.org/I67391869"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Roland Jimenez","raw_affiliation_strings":["Neurocrine Biosciences, Inc., San Diego, California, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neurocrine Biosciences, Inc., San Diego, California, USA","institution_ids":["https://openalex.org/I67391869"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Hui Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I67391869","display_name":"Neurocrine Biosciences (United States)","ror":"https://ror.org/05d84mm26","country_code":"US","type":"company","lineage":["https://openalex.org/I67391869"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hui Zhang","raw_affiliation_strings":["Neurocrine Biosciences, Inc., San Diego, California, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neurocrine Biosciences, Inc., San Diego, California, USA","institution_ids":["https://openalex.org/I67391869"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113490804","display_name":"Dimitri E. Grigoriadis","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I67391869","display_name":"Neurocrine Biosciences (United States)","ror":"https://ror.org/05d84mm26","country_code":"US","type":"company","lineage":["https://openalex.org/I67391869"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dimitri E. Grigoriadis","raw_affiliation_strings":["Neurocrine Biosciences, Inc., San Diego, California, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neurocrine Biosciences, Inc., San Diego, California, USA","institution_ids":["https://openalex.org/I67391869"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5088150542","display_name":"Gordon R. Loewen","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I67391869","display_name":"Neurocrine Biosciences (United States)","ror":"https://ror.org/05d84mm26","country_code":"US","type":"company","lineage":["https://openalex.org/I67391869"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gordon Loewen","raw_affiliation_strings":["Neurocrine Biosciences, Inc., San Diego, California, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neurocrine Biosciences, Inc., San Diego, California, USA","institution_ids":["https://openalex.org/I67391869"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5038729165"],"corresponding_institution_ids":["https://openalex.org/I67391869"],"apc_list":{"value":3350,"currency":"USD","value_usd":3350},"apc_paid":{"value":3350,"currency":"USD","value_usd":3350},"fwci":2.2774,"has_fulltext":true,"cited_by_count":10,"citation_normalized_percentile":{"value":0.87988061,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":93,"max":98},"biblio":{"volume":"12","issue":"4","first_page":"447","last_page":"456"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.4643999934196472,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.4643999934196472,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10023","display_name":"Schizophrenia research and treatment","score":0.11599999666213989,"subfield":{"id":"https://openalex.org/subfields/2738","display_name":"Psychiatry and Mental health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T13561","display_name":"Chemical Reactions and Isotopes","score":0.10000000149011612,"subfield":{"id":"https://openalex.org/subfields/3003","display_name":"Pharmaceutical Science"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/six-membered-heteroarenes","display_name":"six-membered heteroarenes","score":0.9779999852180481},{"id":"https://openalex.org/keywords/valbenazine","display_name":"valbenazine","score":0.9959999918937683},{"id":"https://openalex.org/keywords/dihydrotetrabenazine","display_name":"dihydrotetrabenazine","score":0.8960000276565552},{"id":"https://openalex.org/keywords/tardive-dyskinesia","display_name":"tardive dyskinesia","score":0.9539999961853027},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.8730000257492065},{"id":"https://openalex.org/keywords/stereoisomers","display_name":"stereoisomers","score":0.9049999713897705},{"id":"https://openalex.org/keywords/dopamine-receptors","display_name":"dopamine receptors","score":0.847000002861023},{"id":"https://openalex.org/keywords/serotonin-receptors","display_name":"serotonin receptors","score":0.9879999756813049},{"id":"https://openalex.org/keywords/tetrabenazine","display_name":"tetrabenazine","score":0.6100000143051147},{"id":"https://openalex.org/keywords/drug-metabolism","display_name":"drug metabolism","score":0.6620000004768372},{"id":"https://openalex.org/keywords/radioligand-binding","display_name":"radioligand binding","score":0.7609999775886536},{"id":"https://openalex.org/keywords/intrinsic-clearance","display_name":"intrinsic clearance","score":0.35899999737739563},{"id":"https://openalex.org/keywords/drug-drug-interactions","display_name":"drug-drug interactions","score":0.35499998927116394},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.36000001430511475}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8077540397644043},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3494449257850647}],"mesh":[{"descriptor_ui":"D004298","descriptor_name":"Dopamine","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012701","descriptor_name":"Serotonin","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D013747","descriptor_name":"Tetrabenazine","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D014633","descriptor_name":"Valine","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D018592","descriptor_name":"Cross-Over Studies","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D050493","descriptor_name":"Vesicular Monoamine Transport Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1002/cpdd.1205","doi":"https://doi.org/10.1002/cpdd.1205","is_oa":true,"landing_page_url":"https://doi.org/10.1002/cpdd.1205","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cpdd.1205","source":{"id":"https://openalex.org/S2764863641","display_name":"Clinical Pharmacology in Drug Development","issn_l":"2160-763X","issn":["2160-763X","2160-7648"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","jufo-1","ki-jl-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Clinical Pharmacology in Drug Development","raw_type":"journal-article"},{"id":"pmid:36530055","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/36530055","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Clinical pharmacology in drug development","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1002/cpdd.1205","doi":"https://doi.org/10.1002/cpdd.1205","is_oa":true,"landing_page_url":"https://doi.org/10.1002/cpdd.1205","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cpdd.1205","source":{"id":"https://openalex.org/S2764863641","display_name":"Clinical Pharmacology in Drug Development","issn_l":"2160-763X","issn":["2160-763X","2160-7648"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","jufo-1","ki-jl-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Clinical Pharmacology in Drug Development","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320315137","display_name":"Neurocrine Biosciences","ror":"https://ror.org/05d84mm26"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4311933743.pdf","grobid_xml":"https://content.openalex.org/works/W4311933743.grobid-xml"},"referenced_works_count":37,"referenced_works":["https://openalex.org/W1492552461","https://openalex.org/W1565257873","https://openalex.org/W1591577368","https://openalex.org/W2007721067","https://openalex.org/W2032996897","https://openalex.org/W2040777203","https://openalex.org/W2040867705","https://openalex.org/W2048240991","https://openalex.org/W2051038048","https://openalex.org/W2063487122","https://openalex.org/W2074631079","https://openalex.org/W2093686860","https://openalex.org/W2102395233","https://openalex.org/W2156687558","https://openalex.org/W2166217068","https://openalex.org/W2598837636","https://openalex.org/W2607267818","https://openalex.org/W2609324068","https://openalex.org/W2664149167","https://openalex.org/W2725021787","https://openalex.org/W2744274922","https://openalex.org/W2791001182","https://openalex.org/W2793907994","https://openalex.org/W2889032543","https://openalex.org/W2953926727","https://openalex.org/W2979895092","https://openalex.org/W3012186434","https://openalex.org/W3082177965","https://openalex.org/W3092186603","https://openalex.org/W3102750496","https://openalex.org/W3196915742","https://openalex.org/W4235802159","https://openalex.org/W4298354272","https://openalex.org/W4300633004","https://openalex.org/W4301953634","https://openalex.org/W4389448567","https://openalex.org/W6684219180"],"related_works":["https://openalex.org/W2607267818","https://openalex.org/W2898780717","https://openalex.org/W2744274922","https://openalex.org/W3012186434","https://openalex.org/W7212059498","https://openalex.org/W2609547445","https://openalex.org/W98449988","https://openalex.org/W3185207675","https://openalex.org/W2044660000","https://openalex.org/W4282940452"],"abstract_inverted_index":{"Abstract":[0],"Valbenazine":[1],"and":[2,37,48,71,101,114,128,200],"deutetrabenazine":[3,105,181],"are":[4,173],"vesicular":[5],"monoamine":[6],"transporter":[7],"2":[8],"(VMAT2)":[9],"inhibitors":[10],"approved":[11],"for":[12,97,124,203],"tardive":[13],"dyskinesia.":[14],"The":[15,83,155],"clinical":[16],"activity":[17],"of":[18,35,58,74,110,150,158,167,191,226,229,239],"valbenazine":[19,85],"is":[20,31,38,182,213],"primarily":[21],"attributed":[22],"to":[23,40,175,184],"its":[24],"only":[25,84,148],"dihydrotetrabenazine":[26],"(HTBZ)":[27],"metabolite,":[28,87],"[+]\u2010\u03b1\u2010HTBZ.":[29],"Deutetrabenazine":[30],"a":[32,90,116,214],"deuterated":[33,42],"form":[34],"tetrabenazine":[36],"metabolized":[39,183],"four":[41,185],"HTBZ":[43,86,211],"metabolites:":[44],"[+]\u2010\u03b1\u2010deuHTBZ,":[45],"[+]\u2010\u03b2\u2010deuHTBZ,":[46],"[\u2212]\u2010\u03b1\u2010deuHTBZ,":[47],"[\u2212]\u2010\u03b2\u2010deuHTBZ.":[49],"An":[50],"open\u2010label,":[51],"crossover":[52],"study":[53],"characterized":[54],"the":[55,59,75,136,188,227,240],"pharmacokinetic":[56],"profiles":[57],"individual":[60],"deuHBTZ":[61],"metabolites,":[62],"which":[63,192],"have":[64],"not":[65],"been":[66],"previously":[67],"reported.":[68],"VMAT2":[69,92,119,197,216],"inhibition":[70],"off\u2010target":[72,98,205,223],"interactions":[73],"deuHTBZ":[76,112,139,153,186,244],"metabolites":[77,113],"were":[78],"evaluated":[79],"using":[80],"radioligand":[81],"binding.":[82],"[+]\u2010\u03b1\u2010HTBZ,":[88],"was":[89,115,135,162],"potent":[91,215],"inhibitor,":[93],"with":[94,121,177,196,220],"negligible":[95,194],"affinity":[96,123,202],"dopamine,":[99],"serotonin,":[100],"adrenergic":[102],"receptors.":[103,133,206],"Following":[104],"administration,":[106],"[\u2212]\u2010\u03b1\u2010deuHTBZ":[107],"represented":[108,147],"66%":[109],"circulating":[111,152],"relatively":[117],"weak":[118],"inhibitor":[120,217],"appreciable":[122,201],"dopamine":[125],"(D2S,":[126],"D3)":[127],"serotonin":[129],"(5\u2010HT1A,":[130],"5\u2010HT2B,":[131],"5\u2010HT7)":[132],"[+]\u2010\u03b2\u2010deuHTBZ":[134,168],"most":[137,189],"abundant":[138,190],"metabolite":[140,212],"that":[141,166,180],"potently":[142],"inhibited":[143],"VMAT2,":[144],"but":[145],"it":[146],"29%":[149],"total":[151],"metabolites.":[154,245],"mean":[156],"half\u2010life":[157],"[+]\u2010\u03b1\u2010HTBZ":[159],"(22.2":[160],"hours)":[161],"\u223c3\u00d7":[163],"longer":[164],"than":[165],"(7.7":[169],"hours).":[170],"These":[171],"findings":[172],"similar":[174],"studies":[176],"tetrabenazine,":[178],"in":[179,198,218],"stereoisomers,":[187],"has":[193],"interaction":[195],"vitro":[199,219],"several":[204],"In":[207],"contrast,":[208],"valbenazine's":[209],"single":[210],"no":[221],"discernible":[222],"activity.":[224],"Determination":[225],"effects":[228,241],"intrinsic/extrinsic":[230],"variables":[231],"on":[232,242],"deutetrabenazine's":[233],"safety/efficacy":[234],"profile":[235],"should":[236],"incorporate":[237],"assessment":[238],"all":[243]},"counts_by_year":[{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2023-01-02T00:00:00"}