Renal cortical kinetics of gentamicin after implantation of gentamicin-polymethylmethacrylate beads in rats.

Beads of gentamicin-polymethylmethacrylate (Septopal), each containing 4.5 mg of gentamicin base, were implanted intraperitoneally in rats. Each rat received one bead. Serum levels and urinary excretion of gentamicin were maximal in the first day of treatment (0.6 micrograms/ml in serum 3 h after implantation of the bead and 525 micrograms per 24-h urine sample) and decreased thereafter. Kidney cortical concentrations of gentamicin progressively increased and peaked after 4 days, reaching 117 micrograms/g. Tissue levels decreased thereafter in spite of the persistence of the drug in urine, and this occurred in the absence of cell damage leading to cell death. Release of gentamicin from intact proximal tubular cells, despite continuous uptake, prevented intracellular drug concentrations from reaching a nephrotoxic level. This experimental study provides a rational basis for the previous clinical observation that nephrotoxicity due to treatment with gentamicin-polymethylmethacrylate beads is improbable.