Comparative Ototoxicity of Kanamycin a and Kanamycin B in the Guinea Pig

Abstract

It has previously been shown that simple compounds with multiple amine groups are oto-toxic, 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.

Key Words:

• ototoxicity
• kanamycin A
• kanamycin B