Impact of Subacute Exposure to T-2 Toxin and Zearalenone on the Pharmacokinetics of Midazolam as CYP3A Probe Drug in a Porcine Animal Model: A Pilot Study

In conclusion, ZEA and T-2 have a tendency to influence the pharmacokinetics (PK) of MDZ, a typical CYP3A substrate, at realistic levels of mycotoxin contamination, although the results were only significant for Ke and marginally non-significant for F, and Ka. However, a larger follow-up study should be performed to confirm the current findings. The results of the present study allow to calculate an appropriate sample size for this future research. As DON and ZEA are frequently occurring in food and feed, they can affect pharmacotherapy. Indeed, alterations in biotransformation capacities can lead to an altered exposure and have deleterious effects on therapeutic outcome of substrate drugs. In addition these alterations can potentially lead to toxic responses and longer than expected withdrawal times for some therapeutics. Finally, as porcine and human CYP3A closely resemble each other, co-ingestion of ZEA and T-2 contaminated food with drugs can possibly affect human drug disposition as well. Ethics Statement All procedures performed in the animal trial were in accordance to the ethical standards of the ethical committee of the Faculties of Veterinary Medicine and Bioscience Engineering of Ghent University (Approval No. EC2017_91). Author Contributions All authors wrote the manuscript. WS studied the design and performed the data analysis. Funding This work was supported by the Ghent University Special Research Fund grant BOF DOC.2015.0075. Conflict of Interest Statem...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research