Comparative ototoxicity of kanamycin A and kanamycin B in the guinea pig.

It has previously been shown that simple compounds with multiple amine groups are ototoxic, the degree of ototoxicity depending on the number of amine groups in the molecule. The relationship between the number of amino groups and ototoxicity in aminoglycoside was studied using kanamycin A and kanamycin B, which contain 4 and 5 amino groups respectively. Forty-five pigmented guinea pigs were injected intratympanically with 0.1 ml of different concentrations of kanamycin A and kanamycin B. The animals were sacrificed 4 days after injection and the organ of Corti was studied by scanning electron microscopy. It was found that on an equimolar basis, kanamycin B (with 5 amino groups) is more cochleotoxic than kanamycin A (with 4 amino groups). The greater cochleotoxic potential of kanamycin B may be explained by the higher cationic nature of the molecule due to protonation of the amino--NH2 groups at physiological pH, resulting in a greater affinity between the drug and the cell membrane.