Federspil P, Schätzle W, Tiesler E
Arch Otorhinolaryngol. 1977 Jul 29;217(2):147-66. doi: 10.1007/BF00665534.
The pharmacokinetics of gentamicin, tobramycin, and amikacin in the inner ear fluids and serum of the guinea pig were studied. The concentrations of these antibiotics were determined by a microbiological method and could be confirmed by the use of 14C-labeled gentamicin. Retention was clearly demonstrated in perilymph and endolymph, whereas there was no retention in the cerebrospinal fluid and the compartments of the eye. A linear relation between concentrations in the perilymph and dosage of gentamicin was ascertained. There was no difference between the concentration of drug in endolymph and that in perilymph. The concentrations of these antibiotics in the perilymph were symmetrical and many times higher than those in the brain. Long-term treatment did not influence the pharmacokinetics of the three antibiotics in the inner ear. However, increased levels of drug in the inner ears in animals with uremia and in some animals with otitis media explained the increased ototoxicity that was observed in histological investigations of these two conditions. Cisternal puncture and diuretics did not change the concentrations of aminoglycoside antibiotics in the inner ear. In large experimental series the hair cell degeneration pattern of the new aminoglycoside antibiotics was determined by the surface preparation technique as well as the influence of the different factors upon this pattern. A prophylactic effect on the ototoxicity of the aminoglycoside antibiotics could not be found in the 2,3-dimercaptopropanol, but by dividing the daily dosage administered. Young guinea pigs were generally not very sensitive to gentamicin, in some cases however much more. Late ototoxicity could not be found after administration of gentamicin. The pharmacokinetical and especially the histological investigations allowed an evaluation of the ototoxicity of the new aminoglycoside antibiotics. By histochemical investigations no influence of the new aminoglycoside antibiotics upon the amount of unspecific esterases and alkaline phosphatase in the inner ear could be detected, but an increase of the amount of acid phosphatase in slightly damaged outer hair cells.
研究了庆大霉素、妥布霉素和阿米卡星在豚鼠内耳液和血清中的药代动力学。这些抗生素的浓度通过微生物学方法测定，并用14C标记的庆大霉素进行了验证。外淋巴和内淋巴中明显存在药物潴留，而脑脊液和眼内各腔室中则无药物潴留。确定了外淋巴中庆大霉素浓度与剂量之间的线性关系。内淋巴中药物浓度与外淋巴中药物浓度无差异。这些抗生素在外淋巴中的浓度呈对称分布，且比脑内浓度高许多倍。长期治疗不影响这三种抗生素在内耳中的药代动力学。然而，尿毒症动物和一些中耳炎动物内耳中药物水平升高，解释了在这两种情况下组织学研究中观察到的耳毒性增加现象。脑室穿刺和利尿剂并未改变内耳中氨基糖苷类抗生素的浓度。在大量实验系列中，采用表面制备技术确定了新型氨基糖苷类抗生素的毛细胞变性模式，以及不同因素对该模式的影响。在2,3 - 二巯基丙醇中未发现对氨基糖苷类抗生素耳毒性的预防作用，但通过分次给予每日剂量可起到预防作用。幼年豚鼠一般对庆大霉素不太敏感，但在某些情况下敏感性更高。给予庆大霉素后未发现迟发性耳毒性。药代动力学研究，尤其是组织学研究，有助于评估新型氨基糖苷类抗生素的耳毒性。通过组织化学研究，未检测到新型氨基糖苷类抗生素对内耳中非特异性酯酶和碱性磷酸酶含量的影响，但在轻度受损的外毛细胞中酸性磷酸酶含量增加。
