Gentamicin-specific antiserum alters the disposition of gentamicin by the isolated perfused rat kidney

Previous studies have indicated that antibodies or Fab fragments of antibodies can be used to alter the pharmacologic or toxicologic effects of drugs. The present study was conducted to determine the effect of specific antiserum administration on the renal excretion of a drug with a high nephrotoxic potential (e.g., gentamicin) using the IPK. After a perfusion period during which the renal clearance of gentamicin was determined, either serum or gentamicin-specific antiserum was added to the perfusion medium. Experiments with serum addition served as controls for a comparison of the effects of antiserum addition on gentamicin renal clearance and tissue accumulation. Addition of antiserum decreased the renal clearance and tissue accumulation of gentamicin. Increasing perfusate gentamicin concentrations at the end of the experimental time suggested that these alterations in disposition could be due to the formation of a nonfilterable gentamicin-antiserum complex. The addition of antiserum also rapidly reversed the increasing fractional excretion of potassium ion. Therefore it would appear that a commercially available antiserum is capable of decreasing renal tissue accumulation of gentamicin and that the IPK represents a viable system for studying the effects of antisera on renal drug disposition.