PBPK modeling for lindane across different species

Interspecies differences are one of the important factors to consider when extrapolating a physiologically based pharmacokinetic (PBPK) model from one species to another. As some of the parameters used in PBPK models are not always available from in-vitro/in-vivo experiments or previous literature, it is important to know how to estimate the parameters from one species to another based on some known relationships.  Lindane is a neurotoxicant and has been used as pesticides. It impairs neuronal firing rate, so the concentration in the body becomes important to know. Although it has been banned since 2009, there are still residues remain in the environment and may be accidentally administered by farm animals. In this study, lindane is used to extrapolate rat and human PBPK model to a cow model to estimate the concentration of lindane in several compartments (liver, blood, rapidly perfused tissues, slowly perfused tissue, mammary tissue, adipose tissue and brain)  in cow after a single dose of lindane.

Rat model and human model used for extrapolation are adopted from previous studies. The model predicts the concentration of lindane in tissues during the elimination process. The administrations of lindane were considered as an oral dose. Parameter analysis was done using MATLAB to check if the parameters and the result of the cow model are within an acceptable range. The concentration of lindane within each compartment in the cow is similar to that of human and rat even though some of the physiological parameters such as body weight and cardiac output are significantly different. The model result was compared with several previously published data in rats, human and cow. This finding indicates that the model can be predictive for lindane elimination in cows.

As lindane is a lipophilic pollutant, further modifications of this model from single administration to chronic low dose administration can be used to predict the accumulation of lindane residue in the body.