دورية أكاديمية
Exploring the Impact of Efavirenz on Aflatoxin B1 Metabolism: Insights from a Physiologically Based Pharmacokinetic Model and a Human Liver Microsome Study.
| العنوان: | Exploring the Impact of Efavirenz on Aflatoxin B1 Metabolism: Insights from a Physiologically Based Pharmacokinetic Model and a Human Liver Microsome Study. |
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| المؤلفون: | Lootens O; Centre of Excellence in Mycotoxicology and Public Health, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.; Laboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.; MYTOX-SOUTH®, International Thematic Network, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium., De Boevre M; Centre of Excellence in Mycotoxicology and Public Health, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.; MYTOX-SOUTH®, International Thematic Network, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium., Gasthuys E; Laboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium., De Saeger S; Centre of Excellence in Mycotoxicology and Public Health, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.; MYTOX-SOUTH®, International Thematic Network, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.; Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Doornfontein Campus, P.O. Box 17011, Gauteng 2028, South Africa., Van Bocxlaer J; Laboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium., Vermeulen A; Laboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. |
| المصدر: | Toxins [Toxins (Basel)] 2024 Jun 04; Vol. 16 (6). Date of Electronic Publication: 2024 Jun 04. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101530765 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6651 (Electronic) Linking ISSN: 20726651 NLM ISO Abbreviation: Toxins (Basel) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel : MDPI |
| مواضيع طبية MeSH: | Aflatoxin B1*/pharmacokinetics , Aflatoxin B1*/toxicity , Benzoxazines*/pharmacokinetics , Benzoxazines*/metabolism , Alkynes* , Cyclopropanes* , Microsomes, Liver*/metabolism , Microsomes, Liver*/drug effects , Drug Interactions* , Models, Biological* , Reverse Transcriptase Inhibitors*/pharmacokinetics, Humans ; Male ; Cytochrome P-450 CYP3A/metabolism ; Adult ; Female ; Cytochrome P-450 CYP1A2/metabolism ; Middle Aged ; Young Adult ; White People |
| مستخلص: | Physiologically based pharmacokinetic (PBPK) models were utilized to investigate potential interactions between aflatoxin B1 (AFB1) and efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor drug and inducer of several CYP enzymes, including CYP3A4. PBPK simulations were conducted in a North European Caucasian and Black South African population, considering different dosing scenarios. The simulations predicted the impact of EFV on AFB1 metabolism via CYP3A4 and CYP1A2. In vitro experiments using human liver microsomes (HLM) were performed to verify the PBPK predictions for both single- and multiple-dose exposures to EFV. Results showed no significant difference in the formation of AFB1 metabolites when combined with EFV (0.15 µM) compared to AFB1 alone. However, exposure to 5 µM of EFV, mimicking chronic exposure, resulted in increased CYP3A4 activity, affecting metabolite formation. While co-incubation with EFV reduced the formation of certain AFB1 metabolites, other outcomes varied and could not be fully attributed to CYP3A4 induction. Overall, this study provides evidence that EFV, and potentially other CYP1A2/CYP3A4 perpetrators, can impact AFB1 metabolism, leading to altered exposure to toxic metabolites. The results emphasize the importance of considering drug interactions when assessing the risks associated with mycotoxin exposure in individuals undergoing HIV therapy in a European and African context. |
| فهرسة مساهمة: | Keywords: CYP450 enzymes; LC-MS/MS; aflatoxin B1; efavirenz; human liver microsomes; in vitro; mycotoxins; pharmacokinetics |
| المشرفين على المادة: | 9N2N2Y55MH (Aflatoxin B1) 0 (Benzoxazines) JE6H2O27P8 (efavirenz) 0 (Alkynes) 0 (Cyclopropanes) 0 (Reverse Transcriptase Inhibitors) EC 1.14.14.1 (Cytochrome P-450 CYP3A) EC 1.14.14.1 (CYP1A2 protein, human) EC 1.14.14.1 (Cytochrome P-450 CYP1A2) EC 1.14.14.55 (CYP3A4 protein, human) |
| تواريخ الأحداث: | Date Created: 20240626 Date Completed: 20240626 Latest Revision: 20240626 |
| رمز التحديث: | 20240626 |
| DOI: | 10.3390/toxins16060259 |
| PMID: | 38922153 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2072-6651 |
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| DOI: | 10.3390/toxins16060259 |