Building a human physiologically based pharmacokinetic model for aflatoxin B1 to simulate interactions with drugs
- Author
- Orphélie Lootens (UGent) , Marthe De Boevre (UGent) , Jia Ning, Elke Gasthuys (UGent) , Jan Van Bocxlaer (UGent) , Sarah De Saeger (UGent) and An Vermeulen (UGent)
- Organization
- Abstract
- Mycotoxins such as aflatoxin B1 (AFB1) are secondary fungal metabolites present in food commodities and part of one's daily exposure, especially in certain regions, e.g., sub-Saharan Africa. AFB1 is mostly metabolised by cytochrome P450 (CYP) enzymes, namely, CYP1A2 and CYP3A4. As a consequence of chronic exposure, it is interesting to check for interactions with drugs taken concomitantly. A physiologically based pharmacokinetic (PBPK) model was developed based on the literature and in-house-generated in vitro data to characterise the pharmacokinetics (PK) of AFB1. The substrate file was used in different populations (Chinese, North European Caucasian and Black South African), provided by SimCYP((R)) software (v21), to evaluate the impact of populations on AFB1 PK. The model's performance was verified against published human in vivo PK parameters, with AUC ratios and C-max ratios being within the 0.5-2.0-fold range. Effects on AFB1 PK were observed with commonly prescribed drugs in South Africa, leading to clearance ratios of 0.54 to 4.13. The simulations revealed that CYP3A4/CYP1A2 inducer/inhibitor drugs might have an impact on AFB1 metabolism, altering exposure to carcinogenic metabolites. AFB1 did not have effects on the PK of drugs at representative exposure concentrations. Therefore, chronic AFB1 exposure is unlikely to impact the PK of drugs taken concomitantly.
- Keywords
- PBPK, aflatoxin B1, mycotoxins, IVIVE, DDI, food contaminants, CYTOCHROME-P450 2A13, ACUTE AFLATOXICOSIS, SURFACE-AREA, B-1, METABOLISM, MYCOTOXINS, CYTOTOXICITY, ACTIVATION, OUTBREAK, IMPACT
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01H05DH5A04AVBDE5KDY2A7PZ7
- MLA
- Lootens, Orphélie, et al. “Building a Human Physiologically Based Pharmacokinetic Model for Aflatoxin B1 to Simulate Interactions with Drugs.” PHARMACEUTICS, vol. 15, no. 3, 2023, doi:10.3390/pharmaceutics15030894.
- APA
- Lootens, O., De Boevre, M., Ning, J., Gasthuys, E., Van Bocxlaer, J., De Saeger, S., & Vermeulen, A. (2023). Building a human physiologically based pharmacokinetic model for aflatoxin B1 to simulate interactions with drugs. PHARMACEUTICS, 15(3). https://doi.org/10.3390/pharmaceutics15030894
- Chicago author-date
- Lootens, Orphélie, Marthe De Boevre, Jia Ning, Elke Gasthuys, Jan Van Bocxlaer, Sarah De Saeger, and An Vermeulen. 2023. “Building a Human Physiologically Based Pharmacokinetic Model for Aflatoxin B1 to Simulate Interactions with Drugs.” PHARMACEUTICS 15 (3). https://doi.org/10.3390/pharmaceutics15030894.
- Chicago author-date (all authors)
- Lootens, Orphélie, Marthe De Boevre, Jia Ning, Elke Gasthuys, Jan Van Bocxlaer, Sarah De Saeger, and An Vermeulen. 2023. “Building a Human Physiologically Based Pharmacokinetic Model for Aflatoxin B1 to Simulate Interactions with Drugs.” PHARMACEUTICS 15 (3). doi:10.3390/pharmaceutics15030894.
- Vancouver
- 1.Lootens O, De Boevre M, Ning J, Gasthuys E, Van Bocxlaer J, De Saeger S, et al. Building a human physiologically based pharmacokinetic model for aflatoxin B1 to simulate interactions with drugs. PHARMACEUTICS. 2023;15(3).
- IEEE
- [1]O. Lootens et al., “Building a human physiologically based pharmacokinetic model for aflatoxin B1 to simulate interactions with drugs,” PHARMACEUTICS, vol. 15, no. 3, 2023.
@article{01H05DH5A04AVBDE5KDY2A7PZ7,
abstract = {{Mycotoxins such as aflatoxin B1 (AFB1) are secondary fungal metabolites present in food commodities and part of one's daily exposure, especially in certain regions, e.g., sub-Saharan Africa. AFB1 is mostly metabolised by cytochrome P450 (CYP) enzymes, namely, CYP1A2 and CYP3A4. As a consequence of chronic exposure, it is interesting to check for interactions with drugs taken concomitantly. A physiologically based pharmacokinetic (PBPK) model was developed based on the literature and in-house-generated in vitro data to characterise the pharmacokinetics (PK) of AFB1. The substrate file was used in different populations (Chinese, North European Caucasian and Black South African), provided by SimCYP((R)) software (v21), to evaluate the impact of populations on AFB1 PK. The model's performance was verified against published human in vivo PK parameters, with AUC ratios and C-max ratios being within the 0.5-2.0-fold range. Effects on AFB1 PK were observed with commonly prescribed drugs in South Africa, leading to clearance ratios of 0.54 to 4.13. The simulations revealed that CYP3A4/CYP1A2 inducer/inhibitor drugs might have an impact on AFB1 metabolism, altering exposure to carcinogenic metabolites. AFB1 did not have effects on the PK of drugs at representative exposure concentrations. Therefore, chronic AFB1 exposure is unlikely to impact the PK of drugs taken concomitantly.}},
articleno = {{894}},
author = {{Lootens, Orphélie and De Boevre, Marthe and Ning, Jia and Gasthuys, Elke and Van Bocxlaer, Jan and De Saeger, Sarah and Vermeulen, An}},
issn = {{1999-4923}},
journal = {{PHARMACEUTICS}},
keywords = {{PBPK,aflatoxin B1,mycotoxins,IVIVE,DDI,food contaminants,CYTOCHROME-P450 2A13,ACUTE AFLATOXICOSIS,SURFACE-AREA,B-1,METABOLISM,MYCOTOXINS,CYTOTOXICITY,ACTIVATION,OUTBREAK,IMPACT}},
language = {{eng}},
number = {{3}},
pages = {{17}},
title = {{Building a human physiologically based pharmacokinetic model for aflatoxin B1 to simulate interactions with drugs}},
url = {{http://doi.org/10.3390/pharmaceutics15030894}},
volume = {{15}},
year = {{2023}},
}
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