© 1995 Oxford University Press
research-article |
Comparative Toxicokinetics of Methanol in the Female Mouse and Rat
*Curriculum in Toxicology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7360
Division of Pharmaceutics, School of Pharmacy University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7360
Received July 27, 1994; accepted December 5, 1994
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 (Vmax for elimination, apparent volume of the central compartment [Ve first-order rate constants for intercompartmental transfer [k12 and k21 and first-order absorption rate constants for fast [kAF] and slow [kAS] absorption processes) were compared between species. When normalized for body weight, mice evidenced a higher maximal elimination rate than rats (Vmax=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.