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.

ABSTRACT: Cytochrome P450 enzymes (CYP) are important catalyzing proteins involved in the biotransformation of endogenous and xenobiotic compounds. However, their expression and/or activity can be altered by exposure to contaminants such as mycotoxins. In vitro incubations in porcine hepatic microsomes revealed a potent inhibition of the midazolam (CYP3A) biotransformation by T-2 toxin (T-2) (Ki = 27.0 ± 3.97 μM) and zearalenone (ZEA) (Ki = 1.1 ± 0.22 μM). Consequently, the in vivo impact of 2 weeks exposure to T-2 (1,000 μg/kg feed) or ZEA (500 μg/kg feed) on the pharmacokinetics (PK) of midazolam (MDZ) as a CYP3A probe drug was investigated in pigs, and was compared to a control group receiving no mycotoxins. MDZ was chosen as this drug undergoes substantial first-pass metabolism in

SUBMITTER: Schelstraete W 

PROVIDER: S-EPMC6492070 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature