Comprehensive toxicokinetic analysis reveals major interspecies differences in absorption, distribution and elimination of citrinin in pigs and broiler chickens

Abstract

A comprehensive toxicokinetic analysis of citrinin (CIT) revealed interspecies differences for all toxicokinetic parameters and in absolute oral bioavailability. Oral bioavailability for CIT was complete for broilers (113-131%), while ranging from 37 to 44% in pigs. CIT was more rapidly absorbed in pigs (T_max = 0.92 h) compared to broiler chickens (T_max = 7.33 h). The elimination of CIT was slower in pigs (T_1/2el = 26.81 h after intravenous (IV) administration) compared to chickens (T_1/2el = 1.97 h after IV administration), due to the striking difference in clearance (Cl_iv=9.87 mL/h/kg for pigs versus Cl_iv = 863.09 mL/h/kg for broilers). Also, the volume of distribution differed significantly between pigs (Vd = 0.30 L/kg after IV administration) and chickens (Vd = 2.46 L/kg after IV administration). However, plasma protein binding did not differ statistically significant (91-98%). It is imperative to further investigate biotransformation and elimination pathways in different species, including humans.