The toxicokinetics of methanol in female CD-1 mice and Sprague-Dawley
rats were examined to explore the possibility of species differences i
n 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 gl kg methanol, As expected, the di
sposition of methanol was nonlinear in both species. Data obtained aft
er iv administration of methanol to mice were well described by a one-
compartment model with Michaelis-Menten elimination, Blood methanol co
ncentration-time data after oral administration could be described by
a one-compartment (mice) or two-compartment (rats) model with Michaeli
s-Menten elimination from the central compartment and biphasic absorpt
ion from the gastrointestinal tract, Kinetic parameters (V-max for eli
mination, apparent volume of the central compartment [V-c], first-orde
r rate constants for intercompartmental transfer [k(12) and k(21)], an
d first-order absorption rate constants for fast [k(AF)] and slow [k(A
S)] absorption processes) were compared between species. When normaliz
ed for body weight, mice evidenced a higher maximal elimination rate t
han 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. (C) 1995 Soc
iety of Toxicology.