{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:06:29Z","timestamp":1772118389717,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    In this study, we investigated the combined influence of pregnancy and genetic polymorphisms on efavirenz pharmacokinetics in cervicovaginal fluid (CVF) of women receiving antiretroviral therapy. Women receiving efavirenz\u2010containing antiretroviral therapy were recruited from two hospitals in Nigeria during 2017\u20132020. Sparse CVF and plasma samples were obtained during pregnancy to assess the possible association between drug concentration and\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    polymorphisms (stage I). Participants were stratified into three\n                    <jats:italic>CYP2B6 516G&gt;T (<\/jats:italic>\n                    rs3745274) genotype groups and re\u2010enrolled for intensive pharmacokinetic sampling (stage II). Overall, 159 women (142 pregnant and 12 postpartum) contributed samples in stage I (88 CVF, 81 plasma and 73 paired).\n                    <jats:italic>CYP2B6 516G&gt;T<\/jats:italic>\n                    (rs3745274) remained independently associated with log\n                    <jats:sub>10<\/jats:sub>\n                    efavirenz CVF concentration during pregnancy after adjusting for plasma concentration, with \u03b2 (Log\n                    <jats:sub>10<\/jats:sub>\n                    efavirenz concentration, 95%CI) of 0.204 (0.027, 0.382),\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.025). Median (IQR) efavirenz\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    in CVF during pregnancy (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) vs. postpartum (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) was 243\u2009ng\/mL (168\u2013402) vs. 447\u2009ng\/mL (159\u2013974),\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    was 1,031\u2009ng\/mL (595\u20131,771) vs. 1,618\u2009ng\/mL (675\u20132,695), and AUC\n                    <jats:sub>0\u201024h<\/jats:sub>\n                    was 16,465\u2009ng.h\/mL (9,356\u201330,417) vs. 30,715\u2009ng.h\/mL (10,980\u201343,714). CVF\u2010to\u2010plasma AUC ratio was 0.36 during pregnancy and 0.46 postpartum. Upon stratification, efavirenz clearance during pregnancy was 57.9% higher than postpartum in patients with the\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    516GT genotype; the AUC\n                    <jats:sub>0\u201024h<\/jats:sub>\n                    and\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    were 33.8% and 8.6% lower, respectively. Efavirenz\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    in CVF exceeded the protein binding\u2010adjusted IC\n                    <jats:sub>90<\/jats:sub>\n                    (PBIC\n                    <jats:sub>90<\/jats:sub>\n                    ) of 126\u2009ng\/mL during pregnancy and postpartum. Efavirenz is well distributed into the CVF; both pregnancy and\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    polymorphisms affect the extent of exposure.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3343","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T02:10:21Z","timestamp":1718071821000},"page":"1062-1070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacogenetics of Efavirenz Exposure in Cervicovaginal Fluid during Pregnancy and Postpartum"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8902-4150","authenticated-orcid":false,"given":"Oluwasegun","family":"Eniayewu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences University of Ilorin  Ilorin Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uche","family":"Azuka","sequence":"additional","affiliation":[{"name":"Federal Medical Centre  Makurdi Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonah","family":"Ogah","sequence":"additional","affiliation":[{"name":"Federal Medical Centre  Makurdi Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8671-4965","authenticated-orcid":false,"given":"Ebunoluwa","family":"Adejuyigbe","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Clinical Sciences Obafemi Awolowo University  Ile\u2010Ife Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8295-7150","authenticated-orcid":false,"given":"Oluseye","family":"Bolaji","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Obafemi Awolowo University  Ile\u2010Ife Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6588-5749","authenticated-orcid":false,"given":"Adeniyi","family":"Olagunju","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics University of Liverpool  Liverpool 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