{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T21:04:42Z","timestamp":1784581482301,"version":"3.55.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7]]},"abstract":"\n Background<\/jats:title>\n Coadministration of artemether\u2013lumefantrine and efavirenz has been shown to result in significant interactions. The influence of functional genetic polymorphisms in selected CYPs on the magnitude of this interaction was investigated in pregnant and nonpregnant adults.<\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n A standard 3-day regimen of artemether\u2013lumefantrine was administered to each patient on steady-state efavirenz-based antiretroviral therapy (ART). Pharmacokinetic parameters were obtained from intensive plasma concentration\u2013time data. Genotyping data were tested for compliance with Hardy\u2013Weinberg equilibrium by Chi-square test. Linear regressions, Mann\u2013Whitney U<\/jats:italic>-test or Kruskal\u2013Wallis tests were conducted to examine the association of lumefantrine plasma level with CYP2B6 c.516G>T, NR1I3 152c-1089T>C, CYP2B6 c.983T>C, CYP3A5*3 and CYP3A4*22.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among a total of 69 malaria\u2013HIV coinfected patients (34 nonpregnant and 35 pregnant), median (interquartile range) age was 33 (27\u201336.5) years and body weight was 59.5 (50\u201367.5) kg. In nonpregnant group, CYP2B6<\/jats:italic> c.516G>T was significantly associated with lower log C<\/jats:italic>\n day 7<\/jats:sub> of lumefantrine using multivariate linear regressions (\u03b2<\/jats:italic>\u2009=\u2009\u22120.239; P<\/jats:italic>\u2009=\u20090.013). In 59% of women with CYP2B6 c.516T, C<\/jats:italic>\n day 7<\/jats:sub> of lumefantrine was below the target of 280\u2009ng\/mL compared to 47% in the noncarriers. CYP2B6<\/jats:italic> c.983T>C significantly associated with higher log C<\/jats:italic>\n day 7<\/jats:sub> of desbutyl lumefantrine in both pregnant (\u03b2<\/jats:italic>\u2009=\u20090.383; P<\/jats:italic>\u2009=\u20090.033) and nonpregnant (\u03b2<\/jats:italic>\u2009=\u20090.395; P<\/jats:italic>\u2009=\u20090.023) groups. Composite genotypes for both CYP2B6 Single-nucleotide polymorphisms strongly associated with lumefantrine plasma concentration. An associative trend between lumefantrine pharmacokinetics and NR1I3 152c-1089T>C genotypes indicated that 70% of the C<\/jats:italic>\n day 7<\/jats:sub> of lumefantrine in those with NR1I3<\/jats:italic> 152c-1089TT genotype was below 280\u2009ng\/mL compared to 53% in those with NR1I3<\/jats:italic> 152c-1089CC or CT genotype.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The findings revealed that the efavirenz\u2013lumefantrine interaction was accentuated in the group with CYP2B6<\/jats:italic> c.516T, c.983C and NR1I3<\/jats:italic> 152c-1089T alleles. This warrants further investigations of other drug\u2013drug interactions for optimising dosing in genetically defined subgroups, particularly during drug development.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000401","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T07:06:57Z","timestamp":1585120017000},"page":"96-106","source":"Crossref","is-referenced-by-count":6,"title":["Influence of selected polymorphisms in disposition genes on lumefantrine pharmacokinetics when coadministered with efavirenz"],"prefix":"10.1097","volume":"30","author":[{"given":"Adebanjo Jonathan","family":"Adegbola","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abutaima","family":"Rana","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Zarqa University, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babatunde Ayodeji","family":"Adeagbo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahman A.","family":"Bolarinwa","sequence":"additional","affiliation":[{"name":"Department of Haematology and Immunology, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeniyi Ebenezer","family":"Olagunju","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria"},{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Siccardi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluseye Oladotun","family":"Bolaji","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"R2-20230911","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1016\/S2214-109X(16)30236-4","article-title":"Efficacy and safety of re-treatment with the same artemisinin-based combination treatment (ACT) compared with an alternative ACT and quinine plus clindamycin after failure of first-line 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