Comparative Toxicokinetics of Methanol in the Female Mouse and Rat

Abstract

Comparative Toxicokinetics of Methanol in the Female Mouse and Rat. Ward, K. W., Perkins, R. A., Kawagoe, J. L., and Pollack, G. M. (1995). Fundam. Appl. Toxicol. 26, 258-264. 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-min 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 c], first-order rate constants for intercompartmental transfer [ k 12 and k 21], 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.