In Vitro Adsorption and in Vivo Pharmacokinetic Interaction between Doxycycline and Frequently Used Mycotoxin Binders in Broiler Chickens

Abstract

Mycotoxin binders are readily mixed in feeds to prevent uptake of mycotoxins by the animal. Concerns were raised for nonspecific binding with orally administered veterinary drugs by the European Food Safety Authority in 2010. This paper describes the screening for in vitro adsorption of doxycycline-a broad-spectrum tetracycline antibiotic-to six different binders that were able to bind >75% of the doxycycline. Next, an in vivo pharmacokinetic interaction study of doxycycline with two of the binders, which demonstrated significant in vitro binding, was performed in broiler chickens using an oral bolus model. It was shown that two montmorillonite-based binders were able to lower the area under the plasma concentration-time curve of doxycycline by >60% compared to the control group. These results may indicate a possible risk for reduced efficacy of doxycycline when used concomitantly with montmorillonite-based mycotoxin binders.

Potential adverse effects on animal health and performance caused by the addition of mineral adsorbents to feeds to reduce mycotoxin exposure

“…Bentonite interacted with tylosin and decreased its passage through IPEC-J2 (Devreese et al 2013). Also, an in vitro study on adsorption of doxycycline by six different adsorbents (four montmorillonite based-clay, sepiolite and leonardite-based binder) showed that less than 25% of the initial concentration of doxycycline was detected after 4 h of incubation at 37°C, suggesting that 75% of doxycycline was adsorbed by mineral adsorbents (De Mil et al 2015). Furthermore, the in vitro results were validated using two of the montmorillonites-based clays, to study the pharmacokinetics and oral bioavailability of doxycycline in vivo.…”

Efficacy of Bacillus subtilis ANSB060 Biodegradation Product for the Reduction of the Milk Aflatoxin M1 Content of Dairy Cows Exposed to Aflatoxin B1

“…Common types of mycotoxin binders include calcium montmorillonite clay [5], aluminosilicate clay [6], and yeast cell culture [7]. However, some of these adsorbents may also bind minerals, vitamins, and amino acids in feeds [8], as well as reducing the efficiency of the pharmacokinetics of antibiotics [9]. The use of chemical methods comprising ammoniation, ozonation, and peroxidation in food and feeds is limited as a result of the potential toxicity of chemical residues [10].…”

Biodegradation of Mycotoxins: Tales from Known and Unexplored Worlds

“…Another physical removal strategy is the use of inorganic or organic mycotoxin binders (Ramos et al, 1996 ; Kolosova and Stroka, 2011 ). Although these adsorbing binders have some promising features, some may have adverse nutritional effects due to binding of vitamins and minerals (Huwig et al, 2001 ; Yiannikouris et al, 2006 ) or reducing the efficacy pharmacokinetics of antibiotics (De Mil et al, 2015 ).…”