Comparative toxicokinetics of methanol in the female mouse and rat

The toxicokinetics of methanol in female CD-1 mice and Sprague-Dawley rats were examined to explore the possibility of species differences in the disposition of the compound. Mice received a single dose of 2.5 g/kg methanol either po (by gavage) or iv (as a 1-mm infusion). Rats received a single oral dose of 2.5 g/kg methanol. As expected, the disposition of methanol was nonlinear in both species. Data obtained after iv administration of methanol to mice were well described by a one-compartment model with Michaelis-Menten elimination. Blood methanol concentration-time data after oral administration could be described by a one compartment (mice) or two-compartment (rats) model with Michaelis-Menten elimination from the central compartment and biphasic absorption from the gastrointestinal tract Kinetic parameters (V_max for elimination, apparent volume of the central compartment [V_e first-order rate constants for intercompartmental transfer [k₁₂ and k₂₁ and first-order absorption rate constants for fast [k_AF] and slow [k_AS] absorption processes) were compared between species. When normalized for body weight, mice evidenced a higher maximal elimination rate than rats (V_max=117±3 mg/hr/kg vs 60.7±1.4 mg/hr/kg for rats). The contribution of the fast absorption process to overall methanol absorption also was larger in the mouse than in the rat.