Influence of Starvation on Absorption, Distribution, and Action of Barbital in Mice and Rats

Abstract

The influence of food deprivation on the disposition of barbital during the early phase following administration of the drug was studied in mice and rats. Starvation consisted of withholding solid food, but not water, for 24–72 h in mice, and 72 h in rats. The results show that starvation leads to higher blood concentrations of barbital given intraperitoneally (i.p.) and subcutaneously to mice and rats, and intramuscularly to rats. This effect was observed 2.5–10 min following the injection of the barbiturate. In mice, starvation significantly reduced the interval between injection of the drug and loss of the righting reflex, but it extended the duration of the sleeping period. When barbital was given intravenously, starvation no longer resulted in higher blood concentrations of the drug, although starved mice went to sleep more rapidly than fed controls. At the moment of loss of the righting reflex. starved mice had significantly lower concentrations of barbital in the brain than fed controls. The total blood and plasma volumes of starved animals were moderately increased when expressed as a percentage of the body weight. These results suggest that starvation might influence the early phase of barbital absorption following its parenteral administration. There is also an indication that starvation could induce a state of hypersensitivity of the central nervous system to barbital.