Renal clearance and tissue accumulation of gentamicin

Multiple-dose studies of gentamicin pharmacokinetics were performed in 2 treated patients. After the final dose, serum and urine concentration declined in biphasic fashion with beta half-lives of 87 and 173 hr. Recovery of the total dose administered required urine collection for at least 10 to 20 days after the last dose. A two-compartment model was used to describe the biphasic decline in serum concentrations, to simulate all measured concentrations during treatment, and to predict the amount of gentamicin in the tissue compartment. Analysis of autopsy tissues yielded the predicted amount of drug. A linear two-compartment model adequately quantitates gentamicin disposition until about 4 days after cessation of therapy when gentamicin renal clearance begins to decline because of tubular reabsorption.