A flip-flop model for nitrofurantoin disposition in the rabbit following oral administration

The influence of route of administration on the absorption of nitrofurantoin and the effect of factors influencing the absorption, such as water volume taken with the drug, change of gastric emptying rate, and effect of particle size, were investigated in rabbits. To clarify the absorption behavior of nitrofurantoin, the Martis-Levy method analogous to the Wagner-Nelson method was used to obtain the absorption kinetics of the drug. Moment analysis was also used to estimate the absorption behavior of the drug.The rate constants of absorption following oral administration of the drug were significantly smaller than those of elimination following intravenous administration. The results of moment analysis (based on a linear approximation) showed that the mean residence time following intravenous administration was much less than the mean absorption time of any oral dosage form. These results clearly show that the pharmacokinetic profile of nitrofurantoin following oral administration is of flip-flop type. Although this result was obtained in the rabbit, the implications of a flip-flop situation for the human case are discussed on the basis of the available published data.