{"id":"https://openalex.org/W1521531357","doi":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","title":"Pharmacokinetics of methadone in HIV\u2010positive patients receiving the non\u2010nucleoside reverse transcriptase efavirenz","display_name":"Pharmacokinetics of methadone in HIV\u2010positive patients receiving the non\u2010nucleoside reverse transcriptase efavirenz","publication_year":2002,"publication_date":"2002-01-18","ids":{"openalex":"https://openalex.org/W1521531357","doi":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","mag":"1521531357","pmid":"https://pubmed.ncbi.nlm.nih.gov/11851649","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/1874300"},"language":"en","primary_location":{"id":"doi:10.1046/j.0306-5251.2001.01539.x","doi":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","is_oa":true,"landing_page_url":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.0306-5251.2001.01539.x","source":{"id":"https://openalex.org/S13842274","display_name":"British Journal of Clinical Pharmacology","issn_l":"0306-5251","issn":["0306-5251","1365-2125"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-2","vabb-shw"],"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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"British Journal of Clinical Pharmacology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.0306-5251.2001.01539.x","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5110067580","display_name":"Rosario Calvo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rosario Calvo","raw_affiliation_strings":["Department of Phamacy, School of Pharmacy, University of Washington, Seattle, WA 98195, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Phamacy, School of Pharmacy, University of Washington, Seattle, WA 98195, USA","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036617897","display_name":"John C. Lukas","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I169108374","display_name":"University of the Basque Country","ror":"https://ror.org/000xsnr85","country_code":"ES","type":"education","lineage":["https://openalex.org/I169108374"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"John C. Lukas","raw_affiliation_strings":["Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and","institution_ids":["https://openalex.org/I169108374"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044977738","display_name":"M\u00f3nica Rodr\u00edguez","orcid":"https://orcid.org/0000-0003-0403-9810","observed_orcids":["https://orcid.org/0000-0003-0403-9810"]},"institutions":[{"id":"https://openalex.org/I169108374","display_name":"University of the Basque Country","ror":"https://ror.org/000xsnr85","country_code":"ES","type":"education","lineage":["https://openalex.org/I169108374"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Monica Rodriguez","raw_affiliation_strings":["Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and","institution_ids":["https://openalex.org/I169108374"]}]},{"author_position":"middle","author":{"id":null,"display_name":"M. Angeles Carlos","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I169108374","display_name":"University of the Basque Country","ror":"https://ror.org/000xsnr85","country_code":"ES","type":"education","lineage":["https://openalex.org/I169108374"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"M. Angeles Carlos","raw_affiliation_strings":["Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and","institution_ids":["https://openalex.org/I169108374"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5032661583","display_name":"Elena Su\u00e1rez","orcid":"https://orcid.org/0000-0002-6683-4847","observed_orcids":["https://orcid.org/0000-0002-6683-4847"]},"institutions":[{"id":"https://openalex.org/I169108374","display_name":"University of the Basque Country","ror":"https://ror.org/000xsnr85","country_code":"ES","type":"education","lineage":["https://openalex.org/I169108374"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Elena Suarez","raw_affiliation_strings":["Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain and","institution_ids":["https://openalex.org/I169108374"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4780,"currency":"USD","value_usd":4780},"apc_paid":null,"fwci":0.7084,"has_fulltext":true,"cited_by_count":10,"citation_normalized_percentile":{"value":0.63869413,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":93},"biblio":{"volume":"53","issue":"2","first_page":"212","last_page":"214"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.45260000228881836,"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":0.45260000228881836,"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/T10526","display_name":"HIV/AIDS drug development and treatment","score":0.2485000044107437,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"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/T10576","display_name":"Opioid Use Disorder Treatment","score":0.15060000121593475,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/methadone","display_name":"methadone","score":0.9129999876022339},{"id":"https://openalex.org/keywords/efavirenz","display_name":"efavirenz","score":1.0},{"id":"https://openalex.org/keywords/drug-drug-interactions","display_name":"drug-drug interactions","score":0.8450000286102295},{"id":"https://openalex.org/keywords/hiv-infection","display_name":"HIV infection","score":0.7350000143051147},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.8999999761581421},{"id":"https://openalex.org/keywords/people-who-inject-drugs","display_name":"people who inject drugs","score":0.6629999876022339},{"id":"https://openalex.org/keywords/opioid-maintenance-treatment","display_name":"opioid maintenance treatment","score":0.6110000014305115},{"id":"https://openalex.org/keywords/withdrawal-symptoms","display_name":"withdrawal symptoms","score":0.5720000267028809},{"id":"https://openalex.org/keywords/dose-escalation","display_name":"dose escalation","score":0.6840000152587891},{"id":"https://openalex.org/keywords/volume-of-distribution","display_name":"volume of distribution","score":0.6579999923706055},{"id":"https://openalex.org/keywords/clearance","display_name":"clearance","score":0.7639999985694885},{"id":"https://openalex.org/keywords/inter-individual-variability","display_name":"interindividual variability","score":0.5540000200271606},{"id":"https://openalex.org/keywords/steady-state-pharmacokinetics","display_name":"steady-state pharmacokinetics","score":0.6140000224113464},{"id":"https://openalex.org/keywords/non-nucleoside-reverse-transcriptase-inhibitors","display_name":"non-nucleoside reverse transcriptase inhibitors","score":0.777999997138977},{"id":"https://openalex.org/keywords/antiretroviral-therapy","display_name":"antiretroviral therapy","score":0.6880000233650208}],"concepts":[{"id":"https://openalex.org/C2781432083","wikidata":"https://www.wikidata.org/wiki/Q422645","display_name":"Efavirenz","level":5,"score":0.9497437477111816},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.8895266056060791},{"id":"https://openalex.org/C2778767360","wikidata":"https://www.wikidata.org/wiki/Q179996","display_name":"Methadone","level":2,"score":0.8237611055374146},{"id":"https://openalex.org/C2777351918","wikidata":"https://www.wikidata.org/wiki/Q421559","display_name":"Reverse-transcriptase inhibitor","level":5,"score":0.7488558888435364},{"id":"https://openalex.org/C22979827","wikidata":"https://www.wikidata.org/wiki/Q5137311","display_name":"Cmax","level":3,"score":0.573741614818573},{"id":"https://openalex.org/C139254425","wikidata":"https://www.wikidata.org/wiki/Q1332167","display_name":"Volume of distribution","level":3,"score":0.5481774806976318},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.5360875725746155},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5250415802001953},{"id":"https://openalex.org/C3013748606","wikidata":"https://www.wikidata.org/wiki/Q15787","display_name":"Human immunodeficiency virus (HIV)","level":2,"score":0.3433213233947754},{"id":"https://openalex.org/C2993143319","wikidata":"https://www.wikidata.org/wiki/Q583050","display_name":"Antiretroviral therapy","level":4,"score":0.24166199564933777},{"id":"https://openalex.org/C142462285","wikidata":"https://www.wikidata.org/wiki/Q2528140","display_name":"Viral load","level":3,"score":0.2070792317390442},{"id":"https://openalex.org/C159047783","wikidata":"https://www.wikidata.org/wiki/Q7215","display_name":"Virology","level":1,"score":0.09787118434906006}],"mesh":[{"descriptor_ui":"D000480","descriptor_name":"Alkynes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003521","descriptor_name":"Cyclopropanes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004347","descriptor_name":"Drug Interactions","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":"D008691","descriptor_name":"Methadone","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D009294","descriptor_name":"Narcotics","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D010078","descriptor_name":"Oxazines","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D015658","descriptor_name":"HIV Infections","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D015658","descriptor_name":"HIV Infections","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D018894","descriptor_name":"Reverse Transcriptase Inhibitors","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D048588","descriptor_name":"Benzoxazines","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1046/j.0306-5251.2001.01539.x","doi":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","is_oa":true,"landing_page_url":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.0306-5251.2001.01539.x","source":{"id":"https://openalex.org/S13842274","display_name":"British Journal of Clinical Pharmacology","issn_l":"0306-5251","issn":["0306-5251","1365-2125"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-2","vabb-shw"],"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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"British Journal of Clinical Pharmacology","raw_type":"journal-article"},{"id":"pmid:11851649","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/11851649","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":"British journal of clinical pharmacology","raw_type":"Letter"},{"id":"pmh:oai:pubmedcentral.nih.gov:1874300","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC1874300/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"Br J Clin Pharmacol","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1046/j.0306-5251.2001.01539.x","doi":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","is_oa":true,"landing_page_url":"https://doi.org/10.1046/j.0306-5251.2001.01539.x","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.0306-5251.2001.01539.x","source":{"id":"https://openalex.org/S13842274","display_name":"British Journal of Clinical Pharmacology","issn_l":"0306-5251","issn":["0306-5251","1365-2125"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-2","vabb-shw"],"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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"British Journal of Clinical Pharmacology","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.98580002784729,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W1521531357.pdf","grobid_xml":"https://content.openalex.org/works/W1521531357.grobid-xml"},"referenced_works_count":14,"referenced_works":["https://openalex.org/W1497037168","https://openalex.org/W1836675547","https://openalex.org/W1898849923","https://openalex.org/W1968644601","https://openalex.org/W2002965038","https://openalex.org/W2025627804","https://openalex.org/W2032811036","https://openalex.org/W2039276957","https://openalex.org/W2039834249","https://openalex.org/W2079853768","https://openalex.org/W2081558294","https://openalex.org/W2109597925","https://openalex.org/W4244751616","https://openalex.org/W4300584600"],"related_works":["https://openalex.org/W1898849923","https://openalex.org/W3198038877","https://openalex.org/W2056602829","https://openalex.org/W1970115874","https://openalex.org/W2002809044","https://openalex.org/W1807489848","https://openalex.org/W2131364274","https://openalex.org/W88201490","https://openalex.org/W7097686818","https://openalex.org/W1982992667"],"abstract_inverted_index":{"We":[0],"find":[1],"that":[2,137,427,446,496,563],"the":[3,14,42,45,54,56,65,73,79,96,99,102,163,221,233,242,246,251,263,296,304,316,340,365,368,401,418,422,434,438,443,452,456,494,497,506,527,534,545,577,584,597,603,652,678,701,726,732,740],"work":[4],"titled":[5],"\u2018The":[6],"pharmacokinetics":[7,174,214,317],"of":[8,49,67,75,95,104,147,184,194,211,239,284,312,318,342,370,383,397,421,442,465,470,479,509,536,574,586,615,620,654,656,680,746,755,758,764],"methadone":[9,34,71,127,218,258,290,319,343,371,406,471,510,564,616,748],"in":[10,85,173,217,241,257,280,289,320,335,349,367,375,387,407,451,467,505,515,541,544,552,688,700],"HIV-positive":[11],"patients":[12],"receiving":[13,125],"non-nucleoside":[15,659],"reverse":[16,660],"transcriptase":[17,661],"efavirenz\u2019,":[18],"authored":[19],"by":[20,93,169,176,300,511],"Clarke":[21,113,267,480],"et":[22,114,268,481],"al.":[23,115,269,482],"[1],":[24],"adequately":[25],"describes":[26],"an":[27,309,373,381],"interaction":[28,498,588,604],"with":[29,226,339,377,389,486,554,605,749],"possible":[30,431],"clinical":[31,204],"significance":[32],"between":[33,224,262],"and":[35,78,98,175,179,187,215,228,337,353,395,425,455,572,623,640,682,720],"efavirenz.":[36,512,750],"Nevertheless,":[37],"from":[38,108,248],"a":[39,61,82,150,177,188,207,330,487,568,618,627,716],"pharmacokinetic":[40,519],"viewpoint":[41],"study":[43,62,209,414],"lacks":[44],"exploration":[46],"or":[47,157,531],"discussion":[48],"some":[50],"important":[51,203],"issues.":[52],"In":[53,206,329,703],"introduction":[55],"authors":[57,130,363,598,733],"write,":[58],"\u2018we":[59],"designed":[60],"to":[63,121,140,161,346,351,372,380,432,437,493,503,524,549,611,669,674,710,738],"assess":[64],"effect":[66,464],"efavirenz,":[68,657],"EFV,":[69],"on":[70,90],"pharmacokinetics,":[72],"timing":[74],"withdrawal":[76,230],"symptoms,":[77],"requirement":[80],"for":[81,119,323,405,725,744],"dose":[83,742],"escalation":[84],"methadone\u2019.":[86],"Then,":[87],"based":[88],"only":[89,222,501,576,691],"Cmax":[91,249,681],"(obtained":[92],"inspection":[94],"data)":[97],"area":[100],"under":[101,692],"curve":[103],"plasma":[105,243,355,408,613,670],"levels":[106,614],"(AUC)":[107],"0\u201324":[109],"h":[110],"(noncompartmental":[111],"analysis)":[112],"make":[116],"prescription":[117],"recommendations":[118],"efavirenz":[120,293],"injection":[122],"drug":[123,356],"users":[124,325],"oral":[126,747],"concurrently.":[128],"The":[129,385,477,632],"do":[131,270,490,599],"not":[132,271,307,430,491,537,560,600,708],"discuss":[133,272],"any":[134],"kinetic":[135],"parameter":[136,730],"could":[138,201,276,590,634,734],"serve":[139],"predict":[141,354],"dosification":[142],"schedules":[143],"such":[144,663],"as":[145,567,617,664],"volume":[146],"distribution":[148,181],"after":[149,292],"single":[151],"dose,":[152],"clearance":[153],"at":[154,278,526],"steady":[155,212],"state,":[156],"half-life":[158,193,633],"(in":[159],"order":[160,350],"adjust":[162],"dosage":[164,291,712],"interval).":[165],"Methadone":[166],"is":[167,429,449,500,559,565,602,626,707],"characterized":[168],"large":[170],"interindividual":[171,698],"variation":[172],"rapid":[178,236],"extensive":[180],"phase":[182,191],"(half-life":[183],"2\u20133":[185],"h)":[186,196],"slow":[189],"elimination":[190,546],"(\u03bbz":[192],"15\u201360":[195],"[2,":[197],"3].":[198],"This":[199],"alone":[200],"have":[202],"implications.":[205],"recent":[208,331,413],"[4],":[210],"state":[213],"pharmacodynamics":[216],"maintenance":[219,321],"patients,":[220,444],"difference":[223],"individuals":[225,690],"strong":[227],"weak":[229],"symptoms":[231],"was":[232,298],"significantly":[234],"more":[235,412,551],"hourly":[237],"rate":[238],"decline":[240],"concentration":[244],"within":[245],"period":[247],"until":[250],"next":[252],"dose.":[253],"Also,":[254,315,533],"no":[255,648],"differences":[256],"AUC":[259,297,489,683],"were":[260],"observed":[261],"two":[264],"symptom":[265,313],"extremes.":[266],"this":[273,542,555,704],"possibility":[274,585,595],"which":[275,558,575,596,608,694],"explain,":[277],"least":[279],"part,":[281],"their":[282],"finding":[283],"small":[285],"changes":[286,334,386,525],"(increases)":[287],"required":[288],"(22%)":[294],"although":[295],"reduced":[299],"over":[301],"50%":[302],"(since":[303],"latter":[305],"appears":[306],"be":[308,347,522,550,592],"adequate":[310],"correlate":[311],"severity.)":[314],"treatment":[322,344],"opiate":[324],"show":[326],"adaptive":[327],"changes.":[328],"population":[332,718],"study,":[333],"CL":[336,376,624,641],"V":[338,388,622,639],"time":[341,378,390],"had":[345],"considered":[348],"explain":[352],"concentrations":[357],"during":[358],"continuous":[359],"administration":[360],"[5].":[361],"These":[362],"attributed":[364],"time-dependence":[366],"kinetics":[369],"increase":[374],"due":[379,502,523],"autoinduction":[382],"CYP3A4.":[384],"can":[391,521],"reflect":[392],"both":[393],"up-":[394],"down-regulation":[396],"\u03b11-acid":[398],"glycoprotein":[399],"(AAG),":[400],"major":[402],"binding":[403,607,655],"site":[404],"[6,":[409],"7].":[410],"One":[411],"[8]":[415],"has":[416,472],"evaluated":[417],"quantitative":[419],"importance":[420],"metabolic":[423,440],"pathway":[424],"concludes":[426],"it":[428,706],"adapt":[433],"daily":[435],"doses":[436],"hepatic":[439,507],"activity":[441],"suggesting":[445],"intestinal":[447,468,528],"CYP3A4":[448],"involved":[450],"metabolism":[453,508],"(efavirenz":[454],"other":[457,658],"antiretroviral":[458],"drugs":[459],"are":[460,647,666,684],"administered":[461,566],"orally).":[462],"An":[463],"P-glycoprotein":[466],"absorption":[469],"also":[473,591],"been":[474],"suggested":[475],"[9].":[476],"results":[478],"(Figure":[483],"1":[484],"[1])":[485],"lower":[488,612],"lead":[492,610],"conclusion":[495],"described":[499],"induction":[504],"A":[513],"change":[514],"AUC,":[516],"without":[517,714],"primary":[518],"changes,":[520,540],"level":[529],"(CYP3A4":[530],"glycoprotein).":[532],"fact":[535],"observing":[538],"appreciable":[539,697],"figure,":[543],"slope":[547],"seems":[548],"accord":[553],"last":[556],"mechanism,":[557],"discussed.":[561],"Given":[562],"racemic":[569],"mixture":[570],"(R-(+)-methadone":[571],"S-(\u2013)-methadone":[573],"former":[578],"shows":[579],"significant":[580],"opioid":[581],"receptor":[582],"affinity)":[583],"stereoselective":[587],"[10]":[589],"explored.":[593],"Another":[594],"contemplate":[601],"AAG":[606],"would":[609],"result":[619],"elevated":[621],"(methadone":[625],"low":[628],"extraction":[629],"ratio":[630],"drug).":[631],"again":[635],"remain":[636],"unaltered":[637],"if":[638],"changed":[642],"proportionally":[643],"[11].":[644],"Although":[645],"there":[646],"specific":[649],"data":[650],"about":[651],"degree":[653],"inhibitors,":[662],"GW420867X,":[665],"highly":[667],"bound":[668],"proteins":[671],"(range":[672],"89%":[673],"94%)":[675],"[12].":[676],"Finally,":[677],"ranges":[679],"very":[685],"broad,":[686],"even":[687],"those":[689],"methadone,":[693],"implies":[695],"possibly":[696],"variability":[699],"kinetics.":[702],"situation":[705],"advisable":[709],"establish":[711],"regimens":[713],"performing":[715],"proper":[717],"analysis":[719],"establishing":[721],"subject-specific":[722],"covariate":[723],"models":[724],"parameters.":[727],"With":[728],"these":[729],"estimates":[731],"then":[735],"perform":[736],"simulations":[737],"explore":[739],"appropriate":[741],"intervals":[743],"coadministration":[745],"Dr":[751],"Rosario":[752],"Calvo,":[753],"Department":[754],"Pharmacy,":[756,759],"School":[757],"Mail":[760],"Stop":[761],"357630,":[762],"University":[763],"Washington,":[765],"Seattle,":[766],"WA":[767],"98195,":[768],"USA.":[769],"Tel.:":[770],"206":[771,774],"5436788;":[772],"Fax:":[773],"5433835;":[775],"E-mail:":[776],"[email":[777],"protected]":[778],"Received":[779],"24":[780],"May":[781],"2001,accepted":[782],"9":[783],"October":[784],"2001":[785]},"counts_by_year":[{"year":2015,"cited_by_count":1},{"year":2013,"cited_by_count":1}],"updated_date":"2026-11-10T11:39:43.021295","created_date":"2016-06-24T00:00:00"}