Interlot variability in gentamicin and tobramycin concentration and its possible significance

Aminoglycoside therapy is routinely monitored at many institutions. It is widely known that serum concentrations of gentamicin and tobramycin may differ markedly among patients receiving the same doses of these drugs. One possible source of this variability may be interlot variation in the concentration of these drugs in commercial preparations. A study was designed to evaluate inter- and intralot variation in gentamicin and tobramycin concentrations at the labeled concentrations of 10 and 40 mg/ml. Multiple samples from six to 10 lots of commercially available gentamicin sulfate injection (Elkins-Sinn, Inc.) and tobramycin sulfate injection (Eli Lilly & Co.) were studied at each concentration. The actual percentage concentration of gentamicin in various lots ranged from 101 to 134% of the labeled concentrations; the actual percentage range was 101-109% at 10 mg/ml and 102-134% at 40 mg/ml labeled concentration. The actual percentage concentration of tobramycin in various lots ranged from 103 to 122% of labeled concentration; the actual percentage range was 107-117% at 10 mg/ml and 103-122% at 40 mg/ml labeled concentration. The intralot variation was less than 4% for both drugs at two concentrations. Based on these results, an 80-mg dose may in fact contain 107 mg of gentamicin or 98 mg of tobramycin. This may be clinically important in the care of patients and may at least in part explain the large variation in serum concentrations and difficulty in prediction of dosage requirements from routine monitoring. Furthermore, the available literature on pharmacokinetics, efficacy, and toxicity has not considered this interlot variation in aminoglycoside concentration.(ABSTRACT TRUNCATED AT 250 WORDS)