Fundamentals for ethanol chronopharmacokinetics in nonstarved, serially sampled rats

Fed versus starved rats were investigated for an appropriate model for studying the chronopharmacokinetics of ethanol. A serially independent dosage-sampling regimen was compared with a serially dependent one. Before beginning the pharmacokinetic studies, a number of experimental pharmacologic variables was systematically examined and quantified. When 24-hour starved rats (LD = 12:12 h) were injected intraperitoneally with ethanol at varying intervals during a single 24-hour period in a serially dependent manner, no significant differences in blood-ethanol clearance rates were observed. However, when the same dose was administered to ad-libitum-fed rats in a serially independent study, a prominent circadian rhythm in clearance rates was revealed. Interindividual variance was less with fed rats than with starved ones. These studies indicate that further characterization of this rhythm should employ ad-libitum-fed rats colony (serially independently) sampled.