気道粘膜を介する薬剤吸収に及ぼす鼻汁の影響
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概要
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The absorption of Dibekacin (DKB) through rabbits 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 (20mg/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 atomosphere of 5% CO2 in air for 3 hours at 37°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 compaired with that in the control (P〈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-cystein (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.
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