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FIGURE 7.9 MeOH clearance (Cl) and FA areas under the plasma concen-
tration-time curve (AUC) in male mice and rabbits following a single dose of
0.5 or 2 g/kg MeOH. Cl and AUC values were calculated from the MeOH and
FA pharmacokinetics curves of animals dosed with 0.5 or 2 g/kg MeOH (20%
solution in sterile saline) through an i.p. injection. Saline groups not shown (all
not detectable). Each time point represents the mean of three to six mice or
three rabbits for treated groups. The symbol
indicates measures for rabbit
MeOH Cl and FA AUC that were different from the respective mouse values
(p
0.05). Source: From Sweeting et al. (2010).
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accumulation within 6 hours in primates was fivefold and 43-fold higher
than in rabbits and mice, respectively, with accumulation being 10-fold
higher in rabbits than mice (Figure 7.10). Over 48 hours, FA accumu-
lation was nearly fivefold higher in rabbits than mice (Figure 7.9). Low-
dose MeOH in mice and rabbits resulted in similarly saturated MeOH
elimination in both species, but with approximately twofold higher
clearance rates in mice (Figure 7.9). Furthermore, FA accumulation was
3.8-fold higher in rabbits than mice (Figure 7.9), suggesting that rabbits
more closely than mice reflected primates for in vivo MeOH metabo-
lism, and particularly FA accumulation (Sweeting et al., 2010).
MeOH and FA pharmacokinetics were also studied in two additional
mouse strains: C57BL/6J and C3H mice. In comparison to the previ-
ously mentioned CD-1 mouse study, employing the same acute dosing
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