Effect of Fasting on the Elimination of Barbital and Phenobarbital in Rabbits

The effect of fasting on the elimination of barbital and phenobarbital was studied using non-fasted, partly fasted, and fasted rabbits. The renal excretion rate constants of both barbiturates were markedly low during fasting, while the metabolic rate constants were little affected. To clarify the mechanism of reduction of the renal excretion rate of these drugs, creatinine clearance and barbital clearance were simultaneously measured in fasted and non-fasted rabbits. The magnitude of apparent tubular reabsorption rate of barbital increased on fasting without any change of the glomerular filtration rate. The urinary pH, which affects the fraction of undissociated species in the renal tubules, was measured. The urinary pH decreased slowly from 8.4 in freely fed rabbits to 6.0 at 24 hr and 4.7 at 48 hr affter fasting, and it recovered to the original state within 4 hr after refeeding. Therefore, the fraction of undissociated species of both barbiturates in the tubular urine during fasting becomes much larger than that in fed rabbits. Consequently, the relative tubular reabsorption rate should be higher during fasting. Therefore, it can be concluded that the lower renal excretion rate constant during fasting is due to enhanced reabsorption of undissociated species in the acidic tubular urine.