{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:44:50Z","timestamp":1760550290897,"version":"3.41.2"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Swedish International Development Agency","award":["HIV-2006-031","SWE 2007-270"],"award-info":[{"award-number":["HIV-2006-031","SWE 2007-270"]}]},{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["CT.2005.32030.001"],"award-info":[{"award-number":["CT.2005.32030.001"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The objectives of this study were to characterize the population pharmacokinetics (PK) of efavirenz (EFV) and 8-hydroxy-efavirenz (8OHEFV) in plasma and peripheral blood mononuclear cells (PBMCs) and to explore covariates affecting the PK parameters. Fifty-one patients had steady-state 0-to-24-h concentrations of EFV and 8OHEFV in plasma with corresponding concentrations in PBMCs, while 261 patients had one or two sparse concentrations at 16 \u00b1 1 h postdose at weeks 4 and\/or 16. The pharmacogenetic markers\n            <jats:italic>CYP2B6*6<\/jats:italic>\n            ,\n            <jats:italic>CYP3A5*3<\/jats:italic>\n            ,\n            <jats:italic>CYP3A5*6<\/jats:italic>\n            ,\n            <jats:italic>UGT2B7*2<\/jats:italic>\n            ,\n            <jats:italic>ABCB1<\/jats:italic>\n            (3435C\u2192T, 3842A\u2192G),\n            <jats:italic>OATP1B1*1B<\/jats:italic>\n            , and\n            <jats:italic>OATP1B1*5<\/jats:italic>\n            , the presence of a rifampin-based antituberculosis (anti-TB) regimen, baseline body weight and organ function values, and demographic factors were explored as covariates. EFV concentration data were well described by a two-compartment model with first-order absorption (\n            <jats:italic>\n              K\n              <jats:sub>a<\/jats:sub>\n            <\/jats:italic>\n            ) and absorption lag time (\n            <jats:italic>A<\/jats:italic>\n            <jats:sub>lag<\/jats:sub>\n            ) (\n            <jats:italic>\n              K\n              <jats:sub>a<\/jats:sub>\n            <\/jats:italic>\n            = 0.2 h\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>A<\/jats:italic>\n            <jats:sub>lag<\/jats:sub>\n            = 0.83 h; central compartment clearance [CL\n            <jats:sub>c<\/jats:sub>\n            \/\n            <jats:italic>F<\/jats:italic>\n            ] for\n            <jats:italic>CYP2B6*1\/*1<\/jats:italic>\n            = 18 liters\/h, for\n            <jats:italic>CYP2B6*1\/*6<\/jats:italic>\n            = 14 liters\/h, and for\n            <jats:italic>CYP2B6*6\/*6<\/jats:italic>\n            = 8.6 liters\/h) and PBMCs as a peripheral compartment. EFV transfer from plasma to PBMCs was first order (CL\n            <jats:sub>p<\/jats:sub>\n            \/\n            <jats:italic>F<\/jats:italic>\n            = 32 liters\/h), followed by capacity-limited return (\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            = 4,400 ng\/ml\/h;\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            = 710 ng\/ml). Similarly, 8OHEFV displayed a first-order elimination and distribution to PBMCs, with a capacity-limited return to plasma. No covariate relationships resulted in a significant explanation of interindividual variability (IIV) on the estimated PK parameters of EFV and 8OHEFV, except for\n            <jats:italic>CYP2B6*6<\/jats:italic>\n            genotypes, which were consistent with prior evidence. Both EFV and 8OHEFV accumulated to higher concentrations in PBMCs than in plasma and were well described by first-order input and Michaelis-Menten kinetics removal from PBMCs.\n            <jats:italic>CYP2B6*6<\/jats:italic>\n            genotype polymorphisms were associated with decreased EFV and 8OHEFV clearance.\n          <\/jats:p>","DOI":"10.1128\/aac.00207-17","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T00:40:34Z","timestamp":1496191234000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Population Pharmacokinetic Model Linking Plasma and Peripheral Blood Mononuclear Cell Concentrations of Efavirenz and Its Metabolite, 8-Hydroxy-Efavirenz, in HIV Patients"],"prefix":"10.1128","volume":"61","author":[{"given":"Abiy","family":"Habtewold","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, Union University, Jackson, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Aklillu","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyasu","family":"Makonnen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Getnet","family":"Yimer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif","family":"Bertilsson","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Burhenne","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel S.","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, Union University, Jackson, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"WHO. 2016. 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