Beaubien A R, Desjardins S, Ormsby E, Bayne A, Carrier K, Cauchy M J, Henri R, Hodgen M, Salley J, St Pierre A
Drug Toxicology Division, Health Protection Branch, Frederick G. Banting Building, Ottawa, Ontario, Canada.
Acta Otolaryngol. 1990 May-Jun;109(5-6):345-52. doi: 10.3109/00016489009125154.
The time course of threshold increase in the VIII nerve compound action potential was studied in guinea pigs following amikacin administration at four different constant infusion rates. Despite the wide range of dosing durations required to achieve drug ototoxicity (2-24 days), the full development of both high and low frequency hearing loss was invariably found to be delayed with respect to the time of drug removal. The greatest degree of delayed hearing loss generally occurred within the first 7 days after drug removal, with smaller losses occurring during later time intervals. The delay showed a tendency to decrease as the ototoxic dose was increased. Using the data from the two highest dosing rates, it was estimated that a minimum of 4 days had to elapse before any hearing loss could be detected, once an ototoxic amount of drug had been administered. These data suggest that hearing loss is always substantially delayed with respect to the receipt of an ototoxic dose of amikacin, and that this must be taken into account when conducting animal experiments and when monitoring hearing in patients for the early detection of ototoxicity.
在豚鼠中，以四种不同的恒定输注速率给予阿米卡星后，研究了第八对脑神经复合动作电位阈值升高的时间进程。尽管实现药物耳毒性所需的给药持续时间范围很广（2 - 24天），但高频率和低频率听力损失的完全发展相对于停药时间总是延迟的。最严重程度的延迟性听力损失通常发生在停药后的头7天内，在随后的时间间隔内损失较小。随着耳毒性剂量的增加，延迟有减小的趋势。利用两个最高给药速率的数据估计，一旦给予耳毒性剂量的药物，至少需要4天才能检测到任何听力损失。这些数据表明，听力损失相对于接受耳毒性剂量的阿米卡星总是有显著延迟，并且在进行动物实验以及监测患者听力以早期发现耳毒性时必须考虑到这一点。
