Biomedical Engineering Reference
In-Depth Information
7.2.2 Pharmacokinetics of Methanol and Formic Acid
In light of the substantial species differences in MeOH metabolism
between humans and rodents (see Section 7.2.1 for more details), we
sought to establish if human MeOH metabolism might be better
reflected in rabbits than rodents. The plasma pharmacokinetics of
MeOH and FA were compared in male CD-1 mice, New Zealand
white (NZW) rabbits and cynomolgus monkeys over time (24, 48,
and 6 hours, respectively) following a single i.p. injection of 0.5 or
2 g/kg MeOH or its saline vehicle. Following the 2 g/kg dose, MeOH
exhibited zero-order elimination kinetics in all three species, with
comparable peak plasma concentrations and a 2.5-fold higher clearance
in mice than rabbits (Sweeting et al., 2010) (Figures 7.8 and 7.9). FA
FIGURE 7.8 MeOH and FA disposition in male mice, rabbits, and primates
over a 6-hour time period, following a single dose of 2 g/kg MeOH, plotted on a
semilog scale. MeOH was administered through an i.p. injection as a 20%
solution in sterile saline, and plasma samples were analyzed by GC (mice and
rabbits) or by spectrometry (primates) for MeOH or FA concentrations. Each
time point represents the mean of three to six mice, three rabbits, or three
primates for treated groups. Data points with open symbols represent samples
with a MeOH or FA concentration below the level of detection and were
arbitrarily assigned a value of 0.1mmol/l. Source: From Sweeting et al. (2010).
