Thirteen male subjects received 1 mg of either gentamicin or netilmicin per kg, first intramuscularly and then intravenously. After the intramuscular dose, concentrations of gentamicin in the serum were more variable than those of netilmicin. After the intravenous dose, the distribution phase of netilmicin was twice as rapid as gentamicin. The average half-times of the elimination phase were similar, but there was marked variability among the subjects receiving gentamicin. Serum clearance of netilmicin was more rapid than that of gentamicin and could not be attributed to renal elimination. The data indicate that, after intramuscular administration, netilmicin may produce more predictable blood levels than gentamicin and suggest that the body distribution of netilmicin may differ from that of gentamicin.Netilmicin is a new semisynthetic aminoglycoside (32). Netilmicin is N-ethyl sisomicin, with the substituent attached to 2-deoxystreptamine. Another aminoglycoside in clinical use with a substitution on 2-deoxystreptamine is amikacin, a hydroxyaminobutyric acid derivative of kanamycin A. In vitro testing in our laboratory and others (8-10, 20, 23, 27, 31) indicates that the activity of netilmicin against Enterobacteriaceae, Pseudomonas, and Staphylococcus, in general, approximates that of gentamicin. Serum concentrations in animals and humans are comparable to those of gentamicin (27).Netilmicin appears to have two advantages. First, like amikacin, it is effective against some organisms resistant to gentamicin, including indole-negative proteus and strains that produce aminoglycoside-adenylating enzymes (16,23). Second, animal studies indicate that netilmicin has significantly less oto-and nephrotoxicity than does gentamicin (19, 27; R. E. Brummett and K. E. Fox, Fed. Proc. 35:621, 1976). If reduced toxicity is also found in humans, it will strongly influence the relative usefulness of this agent.Netilmicin is now in the early stages of therapeutic evaluation, and expanded information concerning its pharmacology will be of benefit to physician investigators and their patients. For this reason, we have investigated the disposition of netilmicin in humans.
MATERIALS AND METHODSThirteen adult male graduate students were used in our study. The subjects underwent a complete medical history and psychological evaluation; physical examination; determination of base line blood chemistries (chloride, carbon dioxide, potassium, sodium, blood urea nitrogen and glucose, total protein, serum albumin, calcium, inorganic phosphorus, cholesterol, uric acid, creatinine, total bilirubin, alkaline phosphatase, creatine phosphokinase, lactic dehydrogenase, serum glutamic oxaloacetic transferase); complete blood count; urinalysis, including microscopic urinalysis and determination of creatinine clearance. All subjects were judged free from any recognizable illness by the above parameters. The experimental design of the project and the drugs used were explained, and informed consent was obtained from each individual. The study was appr...