Transepithelial Transport of Levofloxacin in the Isolated Perfused Rat Kidney

Purpose. The transepithelial transport of levofloxacin was evaluatedin the isolated perfused kidney to investigate its renal secretorymechanisms.Methods. Levofloxacin was instantaneously administered into the renalartery together with inulin and Evans blue-labeled albumin, and thesingle-pass dilution curves of the renal venous and urinary outflowwere determined in the absence or presence of various compounds.Kinetic parameters were computed based on non-compartmentmoment analysis.Results. The ratio of fractional excretion to filtration fraction (FE/FF)for levofloxacin was 2.99 ± 0.18, indicating the involvement of tubularsecretion. In the presence of cimetidine and quinolones, the FE/FF oflevofloxacin was significantly decreased and the transepithelial meantransit time (¯T_cell) of levofloxacin was prolonged. The ¯T_cell showed anegative correlation with renal secretion of levofloxacin, while thevolume of distribution of levofloxacin showed no correlation.Conclusions. Transport on the brush-border membrane plays adetermining step in the renal secretion of levofloxacin, and cimetidineand quinolones interact with levofloxacin transport on thebrush-border membrane.