LUNG DISTRIBUTION AND PHARMACOKINETICS OF AEROSOLIZED TOBRAMYCIN
LUNG DISTRIBUTION AND PHARMACOKINETICS OF AEROSOLIZED TOBRAMYCIN
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DOI：
10.1164/ajrccm/147.5.1279
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发表时间：
1993-05-01
期刊：
影响因子：
--
通讯作者：
BARON, D
中科院分区：
文献类型：
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作者：
LECONTE, P;POTEL, G;BARON, D
氨基糖苷类药物常用于治疗与β-内酰胺类药物相关的院内肺炎。不幸的是，静脉给药的氨基糖苷类药物在肺组织中的渗透率仍然很低。在动物模型中，这些药物的雾化作用提供了高肺浓度和低血清水平。5名健康志愿者和5名机械通气患者经气动雾化吸入三百毫克妥布霉素和1毫升Tc-99m-DTPA。然后进行肺核素扫描，并研究血浆和尿药动学。在第二组接受开胸手术的患者中，仅以同样的方式给予300毫克妥布霉素；然后取出健康肺的一段，并测量妥布霉素。在第一组中，核素扫描显示了健康志愿者和呼吸机患者的全肺放射性分布。尿样中含有初始量的5.5%的妥布霉素。妥布霉素在健康志愿者和呼吸机患者的平均血药浓度半衰期分别为8.96h和11.23h。第2组雾化吸入后4h和12h肺组织平均浓度分别为5.5和3.61微克/克。因此，妥布霉素的雾化作用产生了高肺浓度和低血清浓度。
Aminoglycosides are commonly used in the treatment of nosocomial pneumonia in association with beta-lactams. Unfortunately, penetration of intravenously administered aminoglycosides into the lung tissue remains low. In animal models, aerosolization of these drugs provides high lung concentrations and low serum levels. Three-hundred milligrams of tobramycin and 1 ml of Tc-99m-DTPA were administered via a pneumatic nebulizer to five healthy volunteers and to five mechanically ventilated patients. Lung scintigraphy was then performed, and plasma and urine pharmacokinetics were studied. In a second group of patients undergoing thoracic surgery, 300 mg of tobramycin alone were administered in the same way; a fragment of healthy lung was then removed, and tobramycin was measured. In the first group, the scintigraphy showed radioactivity distribution in the whole lungs both in healthy volunteers and in ventilated patients. Urine samples contained 5.5% of the initial amount of tobramycin. The mean serum half-life of tobramycin was 8.96 h in healthy volunteers and 11.23 h in ventilated patients. In the second group, mean lung tissue concentrations were 5.5 and 3.61 mug/g, respectively, 4 and 12 h after nebulization, respectively. Aerosolization of tobramycin thus produced high lung concentrations and low serum levels.