Pharmacology of gentamicin in man.

Abstract

Dosage of gentamicin based upon the weight of the patient (1.5-8 mg/kg per day) produced a wide range of concentrations of the drug in serum. In 10% of patients, the level is potentially toxic, but in 30% it is inadequate for therapy. Concentrations of gentamicin in urine are high, in cerebrospinal fluid low, and in bile, pleural, and pericardial fluid one-half to one-fourth that in the serum. Renal insufficiency requires an altered maintenance dosage. Hemodialysis clears gentamicin at a rate equal to 60% of that at which creatinine is cleared. Individual patterns in the response to dose were observed to be accelerated, typical, or dampened, giving brief high, average, or low levels of drug in serum. A significant inverse relation exists between the level of gentamicin in serum and hematocrit. Studies with radioactive gentamicin (100 ztg/ml) showed that 10% was associated with erythrocytes, 30% with plasma proteins, and 60% in solution. The individual dose-responses emphasize the value of monitoring gentamicin levels in serum during treatment. The optimal clinical benefit from treatment of infections caused by organisms sensitive to gentamicin can be obtained only if the dose used provides a therapeutic, but not a toxic, level in the blood. To achieve this goal, it is essential to have information concerning the factors and conditions that influence the concentration of drug in the plasma and the penetration of the drug into various compartments of body fluids. Because gentamicin is not appreciably metabolized or inactivated in the body, the principal determinants of the level in plasma attained with any given dose are the absorption, binding, distribution, and excretion of the drug. The major, if not the exclusive route of elimination of gentamicin from the body is through the kidneys by glomerular fil