University at Buffalo School of Pharmacy and Pharmaceutical Sciences, New York 14260, USA.
Pharmacotherapy. 2010 Jan;30(1):95-108. doi: 10.1592/phco.30.1.95.
Extended-interval once-daily dosing with the aminoglycoside tobramycin has been proven to be equally efficacious as traditional thrice-daily dosing for treatment of the pulmonary exacerbations of cystic fibrosis in adults and children older than 5 years. The frequencies of acute ototoxicity and nephrotoxicity do not appear to be significantly different between patients treated with once- versus thrice-daily dosing, and the risk of acute nephrotoxicity may actually be lower in pediatric patients when once-daily dosing is used. Long-term studies are needed to fully assess the impact that cumulative treatments with once-daily dosing have on renal and auditory function. An increase in antimicrobial resistance has been suggested with once-daily dosing in the cystic fibrosis population. The extended-interval aminoglycoside dose should be determined based on previous therapeutic drug monitoring. If the patient is aminoglycoside (tobramycin) naïve, a dose of 10 mg/kg once/day is suggested, with the dose adjusted by using therapeutic drug monitoring to individualize therapy.
对于大于 5 岁的成年及儿童囊性纤维化肺部感染患者，与传统的每日三次给药相比，每日一次延长间隔时间给予氨基糖苷类抗生素妥布霉素治疗同样有效。每日一次与每日三次给药患者的急性耳毒性和肾毒性的发生率似乎没有明显差异，而且当使用每日一次给药时，儿科患者发生急性肾毒性的风险实际上可能更低。需要长期研究来充分评估每日一次给药累积治疗对肾功能和听力的影响。有研究提示囊性纤维化患者每日一次给药可能会增加抗菌药物耐药性。应根据之前的治疗药物监测来确定延长间隔时间的氨基糖苷类药物剂量。如果患者之前未使用氨基糖苷类药物（妥布霉素），建议每日一次给予 10mg/kg 的剂量，然后根据治疗药物监测结果调整剂量，以实现个体化治疗。
