Nephrotoxicity of the Constituents of the Gentamicin Complex

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Abstract
Commercial gentamicin C is a mixture of gentamicin C1, C12 and C2. The nephrotoxicity of each of these constituents was compared with that of the gentamicin complex. After 7 days the mean creatinine level in serum was 0.8 mg/dl in rats given C2 and 0.5 mg/dl in rats given C1, C1a or the gentamicin complex (P < 0.001). Toxicity attributable to C1a was not detected until day 14; only minimal toxicity was noted in C1-treated rats after 21 days. Nephrotoxicity caused by the gentamicin complex was similar to that caused by C2. By a new high-pressure liquid chromatographic method, the renal concentration of C1, C1a and C2 was quantified in rats given the gentamicin complex. The results indicated an early, preferential renal accumulation of C2. Subsequently, the C2 content of 12 commercial lots of gentamicin C was measured. The C2 concentration ranged from 12.4-20.1 mg/ml. Experimental nephrotoxicity from gentamicin C is largely the result of the C2 constituent; the concentration of this constituent in commercial preparations of gentamicin varies by as much as 7.7 mg/dl.