A 2'guanidyl derivative of gentamicin (S86451) with reduced nephrotoxicity studies at low and medium dose levels in the rat.

The nephrotoxic potential of S86451 (2'guanidyl, 2'deamino gentamicin C1) has been investigated in Sprague-Dawley rats at 10 and 25 mg/kg, in comparison with gentamicin at 4 and 10 mg/kg. The criteria were (i) the severity of the lysosomal phospholipidosis, as assessed by both biochemical and morphological investigations; (ii) the degree of tubular regeneration, a consequence of the aminoglycoside-induced focal necrosis measured by 3H-thymidine incorporation into kidney cortex DNA. S86451 was found at least 2-5 times less toxic than gentamicin. Thus, this compound should be a safer antibiotic than gentamicin in combating organisms with a similar sensitivity to either drug.