The effect of the variation of urinary pH on the pharmacokinetics of the acidic antibacterial agent, cinoxacin (pKa 4.60), was examined. Urinary pH of 24-h fasted rats remained at about pH 6 during the daytime, while that of nonfasted rats was high (about pH 7.5) in the morning and gradually decreased to a pH similar to that of the fasted rat in the afternoon. The free fraction of cinoxacin in fasted rat sera in the morning was similar to that in nonfasted rats despite the longer half-life of cinoxacin in fasted rats. In the afternoon the free fraction was slightly different despite similar cinoxacin elimination in fasted and nonfasted rats. These findings seemed to exclude the contribution of protein binding from the causes of increased cinoxacin elimination in nonfasted rats in the morning. Elimination rate constants of cinoxacin obtained with a one-compartment open model correlated well with urinary pH 30 min after injection, suggesting that the urinary pH plays a more important role in cinoxacin elimination. When cinoxacin was orally administered to fasted rats at 11:00, the area under the plasma concentration-time curve was threefold larger than in nonfasted rats. As found with the intravenous administration, this difference may be explained by the prolonged half-life caused by decreased urinary pH after fasting. This study revealed the time-dependent elimination of cinoxacin in nonfasted rats, which is related to physiological change of urinary pH caused by food intake.