Gentamicin pharmacokinetics during hemodialysis in patients suffering from chronic renal failure

Because the elimination of gentamicin, a potent aminoglycoside antibiotic, is dependent almost entirely on renal excretion, renal functional impairment drastically changes the pharmacokinetics of this drug. As a first step in the study of the effects of renal insufficiency and the anephric state on the pharmacokinetic parameters of gentamicin, serum and urine levels of this drug were studied after a single intravenous bolus dose during hemodialysis in patients suffering from chronic renal failure. The data were fitted to the two-compartment open model and the appropriate kinetic parameters were calculated with the COMPT computer program modified by Pfeffer. The rate constant of metabolism was estimated from plasma and dialysis rate constants of elimination. The rate of renal excretion was shown to be very weak in patients who were not anuric. The use of the mathematical equations of the two-compartment open model demonstrated that, after a single dose of gentamicin, the percentage of decrease of serum concentration with time does not represent, because of tissue binding retention, the percentage of drug eliminated from the body. It was shown that pharmacokinetic parameters represent a useful tool in the optimization of gentamicin therapy.