Central Hospital Pharmacy, The Hague, The Netherlands; Department of Clinical Pharmacology, Haga Teaching Hospital, The Hague, The Netherlands.
Central Hospital Pharmacy, The Hague, The Netherlands; Department of Clinical Pharmacology, Haga Teaching Hospital, The Hague, The Netherlands.
J Cyst Fibros. 2015 Nov;14(6):748-54. doi: 10.1016/j.jcf.2015.01.002. Epub 2015 Jan 27.
The clinical effectiveness of inhaled tobramycin depends on the dose reaching the desired regions of the lungs. This study evaluates the influence of breathing mode on tobramycin lung deposition using its pharmacokinetics as surrogate for deposition.
In a randomized, open-label, crossover study lung deposition in 18 adult CF patients is evaluated following inhalation of tobramycin aerosol using the I-neb nebulizer with TBM (Tidal Breathing Mode) and TIM (Target Inhalation Mode) breathing patterns. Breathing in TIM forced the patient to inhale in a slow and deep manner. Patients were categorized in three subgroups according to their lung function: ≤59%, 60-79% or ≥80% of FEV1 predicted. Blood samples were collected in order to model tobramycin pharmacokinetics. Nebulization time was recorded.
Inhalation with TIM resulted in significantly higher maximum serum levels and area under the concentration-time curves (0-24h). Mean bioavailability of TIM relative to TBM was 1.53±0.41. Mean nebulization time was reduced by half with TIM. Subgroup category did not affect the results.
Slow and deep inhalation of aerosolized tobramycin resulted in higher lung deposition and shorter nebulization time compared to tidal breathing, regardless of the disease severity of the CF patient. Dutch trial register number NTR3109.
吸入妥布霉素的临床疗效取决于到达肺部目标区域的剂量。本研究通过其药代动力学作为沉积的替代物来评估呼吸模式对妥布霉素肺部沉积的影响。
在一项随机、开放标签、交叉研究中，使用 I-neb 雾化器，通过 TBM（潮式呼吸模式）和 TIM（目标吸入模式）呼吸模式，评估了 18 例成年 CF 患者吸入妥布霉素气雾剂后的肺部沉积情况。TIM 中的呼吸迫使患者以缓慢而深入的方式吸入。根据其肺功能将患者分为三组：FEV1 预测值的 ≤59%、60-79%或 ≥80%。采集血样以建立妥布霉素药代动力学模型。记录雾化时间。
TIM 吸入导致的最大血清水平和浓度-时间曲线下面积（0-24 小时）显著升高。TIM 相对于 TBM 的平均生物利用度为 1.53±0.41。TIM 使雾化时间缩短了一半。亚组类别不影响结果。
与潮式呼吸相比，无论 CF 患者的疾病严重程度如何，吸入雾化妥布霉素时缓慢而深入的呼吸都会导致更高的肺部沉积和更短的雾化时间。荷兰试验注册号 NTR3109。
