After intramuscular administration of gentamicin sulfate, peak serum concentrations usually occur between 30 and 60 minutes and serum levels are measurable for 6 to 8 hours. In infants, a single dose of 2.5 mg/kg usually provides a peak serum level in the range of 3 to 5 mcg/mL.When gentamicin is administered by intravenous infusion over a two-hour period, the serum concentrations are similar to those obtained by intramuscular administration. Age markedly affects the peak concentrations: in one report, a 1 mg/kg dose produced mean peak concentrations of 1.58, 2.03, and 2.81 mcg/mL in patients six months to five years old, 5to 10 years old, and over10 years old, respectively.

In infants one week to six months of age, the half-life is 3 to 3½ hours. In full-term and large premature infants less than one week old, the approximate serum half-life of gentamicin is 5½ hours. In small premature infants, the half-life is inversely related to birth weight. In premature infants weighing less than 1500 grams, the half-life is 11½ hours; in those weighing 1500 to 2000 grams, the half-life is eight hours; in those weighing over 2000grams, the half-life is approximately five hours.While some variation is to be expected due to a number of variables such as age, body temperature, surface area and physiologic differences, the individual patient given the same dose tends to have similar levels in repeated determinations.

Gentamicin, like all aminoglycosides, may accumulate in the serum and tissues of patients treated with higher doses and/or for prolonged periods, particularly in the presence of impaired or immature renal function. In patients with immature or impaired renal function, gentamicin is cleared from the body more slowly than in patients with normal renal function.The more severe the impairment, the slower the clearance. (Dosage must be adjusted.)

Since gentamicin is distributed in extracellular fluid, peak serum concentrations may be lower than usual in patients who have a large volume of this fluid. Serum concentrations of gentamicin in febrile patients may be lower than those in afebrile patients given the same dose. When body temperature returns to normal, serum concentrations of the drug may rise. Febrile and anemic states may be associated with a shorter than usual serum half-life. (Dosage adjustment is usually not necessary.) In severely burned patients, the half-life may be significantly decreased and resultingserumconcentrationsmaybelowerthan anticipated from the mg/kg dose.

Protein-binding studies have indicated that the degree of gentamicin binding is low, depending upon the methods used for testing, this may be between 0 and 30%.

In neonates less than three days old, approximately 10% of the administered dose is excreted in 12 hours; in infants 5 to 40 days old, approximately 40% is excreted over the same period. Excretion of gentamicin correlates with postnatal age and creatinine clearance. Thus, with increasing postnatal age and concomitant increase in renal maturity, gentamicin is excreted more rapidly. Little, ifany, metabolic transformation occurs; the drug is excreted principally by glomerular filtration. After several days of treatment, the amount of gentamicin excreted in the urine approaches, but does not equal, the daily dose administered. As with other aminoglycosides, a small amount of the gentamicin dose may be retained in the tissues, especially in the kidneys. Minute quantities of aminoglycosides have been detected in the urine of some patients weeks after drug administration was discontinued. Renal clearance of gentamicinis similar to that of endogenous creatinine.

In patients with marked impairment of renal function, there is a decrease in the concentration of aminoglycosides in urine and in their penetration into defective renal parenchyma. This decreased drug excretion, together with the potential nephrotoxicity of aminoglycosides, should be considered when treating such patients who have urinary tract infections.

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