Comparative Uptake and Lysosomal Phospholipidosis Induced by Gentamicin Components C1, C1a, and C2

Aminoglycosides are nephrotoxic and this adverse effect has triggered many efforts towards the design and/or the screening of less toxic derivatives (see Price, 1986 for a recent review). Yet, the first broad-spectrum and still widely used aminoglycoside, gentamicin, is not a pure substance and is actually commercialized as a mixture of three main components, C1, C1a and C2, which differ by the methylation of the N6 and C6 atoms in the 2’,6’ diaminosugar moiety. Surprisingly enough, little information is available concerning the relative nephrotoxicities of these components. Whereas some reports suggest that gentamicin C1 induces less nephrotoxicity than gentamicin complex in humans (see e.g., Mossegaard et al., 1975) , others failed to substantiate such difference (e.g., Forrey et al., 1978). Kohlepp et al. (1984) showed in a comparative study in rats that gentamicin C2 and gentamicin C1a are more nephrotoxic than gentamicin C1 at an equivalent, high dosage (40 mg/kg). The uptake of gentamicin complex by rat kidney cortex, however, is saturable, with an apparent Km in a 10–20 mg/k serum concentration range (Gauliano et al., 1986).