Hayashi H
Department of Otolaryngology, Mie University School of Medicine.
Nihon Jibiinkoka Gakkai Kaiho. 1990 Jan;93(1):40-9. doi: 10.3950/jibiinkoka.93.40.
The absorption of Dibekacin (DKB) through rabbit's tracheal mucosa with and without nasal mucus were examined in vitro. The modified double chamber method was used for the purpose of this study. DKB solution (20 mg/ml) and Hanks' balanced salt solution were put into the donor compartment (DC) and the receiver compartment (RC), respectively. A plate with a hole and the tracheal mucosa were inserted between the compartments in the order of DC, dialytic membrane, the plate, the rabbit tracheal mucosa and RC. The hole of the plate was filled with nasal mucus or Hanks' solution. The latter was used as the control. The chamber was incubated in a humidified atmosphere of 5% CO2 in air for 3 hours at 37 degrees C. The absorption rate (AR) was obtained by dividing the concentration of DKB in RC by that in DC. The nasal mucus from patients with chronic sinusitis significantly decreased the AR of DKB compared with that in the control (P less than 0.05). The AR significantly decreased with increments in the thickness of nasal mucus by chronic sinusitis. This decreased AR was improved by the addition of N-Acetyl-L-cysteine (NAC) to DKB solution in DC. NAC can cleave disulfied bonds of mucus glycoprotein and this results in the decrease of viscoelasticity of nasal mucus. The results indicate that nasal mucus by chronic sinusitis intercept the absorption of drugs through respiratory epithelium in vitro. One of the mechanisms of the intercepter may be due to the high molecular-reticular structure of nasal mucus.
在体外研究了带和不带鼻黏液的情况下,地贝卡星(DKB)通过兔气管黏膜的吸收情况。本研究采用改良双室法。将DKB溶液(20mg/ml)和汉克斯平衡盐溶液分别放入供体室(DC)和受体室(RC)。在各室之间依次插入一块有孔板和气管黏膜,顺序为DC、透析膜、板、兔气管黏膜和RC。板上的孔用鼻黏液或汉克斯溶液填充。后者用作对照。将该室在含5%二氧化碳的空气潮湿环境中于37℃孵育3小时。吸收速率(AR)通过将RC中DKB的浓度除以DC中DKB的浓度获得。与对照组相比,慢性鼻窦炎患者的鼻黏液显著降低了DKB的AR(P<0.05)。随着慢性鼻窦炎导致的鼻黏液厚度增加,AR显著降低。在DC中的DKB溶液中添加N-乙酰-L-半胱氨酸(NAC)可改善这种降低的AR。NAC可裂解黏液糖蛋白的二硫键,这导致鼻黏液的粘弹性降低。结果表明,慢性鼻窦炎产生的鼻黏液在体外会阻碍药物通过呼吸道上皮的吸收。这种阻碍的机制之一可能是由于鼻黏液的高分子网状结构。