Animal experiments have shown the incidence of amikacin ototoxicity to be a sigmoid function of cumulative plasma AUC regardless of plasma levels. They further suggest that the key determinant of ototoxicity is cumulative perilymph AUC, which is directly proportional to both cumulative plasma AUC and total dose. Hence, both cumulative plasma AUC and total dose estimate the likelihood of ototoxicity, but the former is superior since it takes into account individual differences in plasma levels.
There are not enough human data for any aminoglycoside antibiotic yet to accurately estimate the sigmoid curve relating the incidence of ototoxicity to cumulative serum AUC or total dose. It is possible, however, to calculate a sigmoid relationship of incidence of ototoxicity to kanamycin total dose based on rough estimates from previous publications of human data.
Although these results have yet to be fully verified in humans and for all aminoglycoside antibiotics, it would seem wise to take steps to ensure that dosing adjustments adequately compensate for the increased serum AUC that would occur in patients with reduced renal function.
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