19970825The plasma concentration of fleroxacin (FLRX) was significantly lower (P<0.05) than the control at 0.5 and 1 hour but was significantly (P<0.05) higher at 4, 8, 12 and 24 hurs after the simultaneous oral administration of FLRX with sodium valproate (VPA). The pharmacokinetic parameters, the volume of distribution (Vd) and the area under the plasma concentration-time curve from 0 to 24 hours (AUC0→24) were 1.2-and 2.3-times higher, while the elimination half-life (T1/2) and time to maximum plasma concentration (Tmax), were delayed by 2.9-and 2.6-times after the simultaneous administration with VPA and all changes were significant (P<0.05). In addition, the absorption rate constant (Ka) and clearanse (CL) were, in contrast, 0.5 and 0.5 times lower than the control, and the difference was also significant (P<0.05). The unbound flaction (%) of FLRX in the plasma increased 54 to 80% at 2 minutes and to 76% at 15 minutes after the intravenous administration of VPA. On the other hand, the total levels of FLRX decreased by 31.9 and 27.7% at 2 and 15 minutes after the intravenous administration of VPA, respectively. The urinary concentration of FLRX, demethyl-FLRX and FLRX N-oxide decreased by 50, 40 and 50%, respectively, at 8 hours after the intravenous administration of VPA. These results that VPA may decrease the protein binding and inhibit the metabolic rate of FLRX simultaneously, when they are administered concurrently.