Methyl Mercury Pharmacokinetics In Man: A 5-Compartment Hybrid Model

A 5-compartment hybrid model that simulates the pharmacokinetic behavior of methyl mercury [MeHg] and its biotransformation [demethylation] product inorganic mercury [Hg(II)] in humans is described.This model accounts for demethylation of MeHg at two sites; one which is within the body and a second which is extracorporeal (presumably the gut lumen). Simulations indicate that approximately 85% of demethylation occurs in the gut lumen and 15% in body tissues.The 2-compartment model for Hg(II) pharmacokinetics developed by Farris et al. (2008) serves as the basis for the 5-compartment model and is embedded within its structure. Parameters from the 2-compartment model are used to describe Hg(II) pharmacokinetics in the current model.The model is validated against previously published (Smith et al. 1994) experimental data for two human subjects dosed with MeHg.Model simulations showing the effects of decreased biotransformation of MeHg in the gastrointestinal lumen are discussed.