在机械通气的健康绵羊模型中，静脉注射和雾化给予妥布霉素的肺部药代动力学。

Lung Pharmacokinetics of Tobramycin by Intravenous and Nebulized Dosing in a Mechanically Ventilated Healthy Ovine Model.

机构信息

From the University of Queensland Centre for Clinical Research, Faculty of Medicine (J.A.D., J. Cohen, S.L.P., S.C.W., C.B., J.A.R.) Critical Care Research Group (J.A.D., S.D., J. Chaudhary, J.F.F.) Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy (J.A.R.), The University of Queensland, Brisbane, Australia Department of Intensive Care Medicine (J.A.D., J. Cohen, J.A.R.) Department of Pharmacy (J.A.R.), Royal Brisbane & Women's Hospital, Brisbane, Australia Institute of Health and Biomedical Innovation & School of Public Health and Social Work, Queensland University of Technology, Kelvin Grove, Brisbane, Australia (A.B.) Department of Anaesthesiology and Intensive Care, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden (M.C.) the Pierre Garraud Hospital, Civil Hospitals of Lyon, Lyon, France (C.B.) the National Center for Scientific Research 5558, Biometrics Laboratory and Evolutionary Biology, Claude Bernard University Lyon 1, Lyon, France (C.B.).

出版信息

Anesthesiology. 2019 Aug;131(2):344-355. doi: 10.1097/ALN.0000000000002752.

DOI:10.1097/ALN.0000000000002752

PMID:31107274

Abstract

BACKGROUND

Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs.

METHODS

Ten anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis samples were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h.

RESULTS

The peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637; interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P < 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P < 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P < 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P < 0.001).

CONCLUSIONS

Compared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.

摘要

背景

雾化抗生素可用于治疗呼吸机相关性肺炎。在之前的药代动力学研究中，从未报道过肺间质腔液的浓度。本研究的目的是比较健康肺机械通气绵羊静脉内和雾化妥布霉素在肺间质腔液、上皮衬里液和血浆中的浓度。

方法

10 只麻醉和机械通气的健康绵羊接受了上、下肺叶和颈静脉微透析导管的外科插入。5 只绵羊给予静脉内妥布霉素 400mg，5 只给予雾化妥布霉素 400mg。每 20 分钟收集一次微透析样本，持续 8 小时。在 1 小时和 6 小时时进行支气管肺泡灌洗。

结果

静脉内妥布霉素的峰值肺间质腔液浓度较低，为 20.2mg/L（四分位距，12mg/L，26.2mg/L），而雾化途径为 48.3mg/L（四分位距，8.7mg/L，513mg/L），P=0.002。对于雾化妥布霉素，1 小时时上皮衬里液浓度中位数高于间质腔液浓度（1637；四分位距，650，1781，与 16mg/L，四分位距，7，86，P<0.001）和 6 小时（48，四分位距，17，93，与 4mg/L，四分位距，2，9，P<0.001）。对于静脉内妥布霉素，1 小时时上皮衬里液浓度中位数低于间质腔液浓度（0.19，四分位距，0.11，0.31，与 18.5mg/L，四分位距，9.8，23.4，P<0.001）和 6 小时（0.34，四分位距，0.2，0.48，与 3.2mg/L，四分位距，0.9，4.4，P<0.001）。