Gentamicin pharmacokinetic changes in induced acute canine nephrotoxic glomerulonephritis

Most clinical schemes used to adjust gentamicin dosage regimens in renal insufficiency assume that the volume of distribution remains constant. The purpose of this investigation was to determine the pharmacokinetic parameters of gentamicin (two-compartment open model) before and at two points during the acute phase of experimentally induced nephrotoxic (injection of anti-glomerular basement membrane antibody) glomerulonephritis in beagle dogs. Disease was verified by decreased 24-h creatinine clearance, increased 24-h urinary protein excretion, and characteristic immunofluorescent, light- and electron-microscopic lesions. After disease induction, the concentration of drug in serum at time zero (Cp0) was significantly decreased and the volume of the central compartment (Vc) and the volume of distribution (Vd(area)) were increased in all treated dogs. These findings suggest that the assumption of unchanged volume of distribution in acute glomerulonephritis could lead to a serious overestimation of serum drug concentration.