{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T22:59:30Z","timestamp":1789340370603,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T00:00:00Z","timestamp":1232496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:p> <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Cytochrome P450 (<jats:italic>CYP<\/jats:italic>) <jats:italic>2B6<\/jats:italic> polymorphisms, particularly c.516G\u2192T, are strongly associated with plasma efavirenz concentrations, but do not entirely explain interindividual variability in efavirenz exposure.<\/jats:p><jats:p>\u2022\u2003<jats:italic>In vitro<\/jats:italic> data suggest that CYP2A6 is involved in the metabolism of efavirenz.<\/jats:p><jats:p>\u2022\u2003Rifampicin can induce the function and activity of the main metabolizing for efavirenz and causes small (22\u201326%) reductions in efavirenz area under the curve during co\u2010administration, although with wide interindividual variability.<\/jats:p><jats:p> <jats:bold>WHAT THIS STUDY ADDS<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Identifies <jats:italic>CYP2B6<\/jats:italic> 516G\u2192T polymorphism and carriers of <jats:italic>CYP2A6<\/jats:italic>*<jats:italic>9B<\/jats:italic> and\/or *<jats:italic>17<\/jats:italic> variants as independent predictors of efavirenz mid\u2010dose concentration in human immunodeficiency virus\u2010infected patients.<\/jats:p><jats:p>\u2022\u2003Factors such as concurrent therapy with rifampicin\u2010containing tuberculosis regimen, gender and body mass index had no a significant influence on efavirenz mid\u2010dose concentration.<\/jats:p><jats:p>\u2022\u2003Provides <jats:italic>in vivo<\/jats:italic> evidence that CYP2A6 is likely to be involved in the metabolism of efavirenz.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold> Interindividual variability in efavirenz pharmacokinetics is not entirely explained by the well\u2010recognized <jats:italic>CYP2B6<\/jats:italic> 516G\u2192T single nucleotide polymorphism. The aim of this study was to determine whether polymorphisms in the <jats:italic>CYP2A6<\/jats:italic> gene can be used to enhance the predictability of efavirenz concentrations in human immunodeficiency virus (HIV)\u2010infected native African patients.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> Mid\u2010dose efavirenz plasma concentrations were determined at 4 and 8 weeks following initiation of antiretroviral therapy in 65 HIV\u2010infected Ghanaian patients. Selected CYP2B6 and CYP2A6 genotypes were determined by commercial 5\u2032\u2010nuclease assays. Relationships between averaged 4\u2010 and 8\u2010week mid\u2010dose efavirenz concentrations, demographic variables and genotypes were evaluated by univariate and multivariate statistical approaches including gene\u2013gene interactions.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>  <jats:italic>CYP2B6<\/jats:italic> c.516G\u2192T, <jats:italic>CYP2B6<\/jats:italic> c.983T\u2192C, <jats:italic>CYP2A6<\/jats:italic>*9B and <jats:italic>CYP2A6<\/jats:italic>*17 allele frequencies were 45, 4, 5 and 12%, respectively. Rifampicin therapy, gender, age and body mass index had no significant influence on efavirenz mid\u2010dose concentrations. Median efavirenz concentrations were more than five times higher (<jats:italic>P<\/jats:italic> &lt; 0.001) in patients with <jats:italic>CYP2B6<\/jats:italic> c.516TT genotype compared with GG and GT genotypes. Although none of the <jats:italic>CYP2A6<\/jats:italic> genotypes was associated with altered efavirenz concentrations individually, <jats:italic>CYP2A6<\/jats:italic>*9B and\/or <jats:italic>CYP2A6<\/jats:italic>*17 carriers showed a 1.8 times higher median efavirenz concentration (<jats:italic>P<\/jats:italic>= 0.017) compared with noncarriers. Multiple linear regression analysis indicated that the <jats:italic>CYP2B6<\/jats:italic> c.516G\u2192T polymorphism and <jats:italic>CYP2A6<\/jats:italic> slow\u2010metabolizing variants accounted for as much as 36 and 12% of the total variance in efavirenz concentrations, respectively.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold> Our findings support previous work showing efavirenz oxidation by <jats:italic>CYP2A6<\/jats:italic>, and suggest that both <jats:italic>CYP2A6<\/jats:italic> and <jats:italic>CYP2B6<\/jats:italic> genotyping may be useful for predicting efavirenz plasma concentrations.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2009.03368.x","type":"journal-article","created":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T16:50:50Z","timestamp":1232556650000},"page":"427-436","source":"Crossref","is-referenced-by-count":101,"title":["<i>CYP2B6<\/i> (c.516G\u2192T) and <i>CYP2A6<\/i> (*9B and\/or *17) polymorphisms are independent predictors of efavirenz plasma concentrations in HIV\u2010infected patients"],"prefix":"10.1111","volume":"67","author":[{"given":"Awewura","family":"Kwara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Lartey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwamena W.","family":"Sagoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naser L.","family":"Rzek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Court","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4]]},"reference":[{"key":"e_1_2_7_2_2","unstructured":"US Department of Health and Human Services (DHHS) Panel on Antiretroviral Guideline for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents. 29 January 2008. 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