Nebulizer delivery of tobramycin to the lower respiratory tract

Weber, Allan; Smith, Arnold L.; Williams‐Warren, Judy; Ramsey, Bonnie W.; Covert, David S.

doi:10.1002/ppul.1950170511

Cited by 23 publications

(13 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(3)(4)(5) Although these single-dose studies suggested a short sputum half-life, we found evidence of potential tobramycin accumulation in respiratory secretions with repeated dosing in CF patients < 6 years old. (6) In that trial of TSI 300 mg twice daily for 28 days followed by bronchoalveolar lavage (BAL), tobramycin was detectable in the epithelial lining fluid (ELF) an average of 12 hr after the last dose, at a mean [standard deviation (SD)] concentration of 74 (50) lg/mL.…”

mentioning

confidence: 84%

“…(24) The high degree of variability in peak and trough tobramycin concentrations in the current study is an expected finding that has been observed in all prior pharmacokinetic studies. (3)(4)(5)7,12,25) Importantly, despite the observed variability, peak concentrations were generally in the bactericidal range as described above. In the current study, several participants had higher trough than peak tobramycin concentrations.…”

mentioning

confidence: 90%

“…At the study visit, a trough sample was collected immediately preceding administration of a TSI dose, and a peak sample was collected 15 min after TSI administration. (3,4) The TSI dose at the study visit was administered via Pari LC Plus nebulizer and Pulmo-Aide Ò compressor (DeVilbiss Healthcare, Somerset, PA). Prior to collection of each trough or peak sample, participants performed three oral rinses with sterile saline and then expectorated to remove residual oral tobramycin.…”

Section: Methodsmentioning

confidence: 99%

“…(10,11) Prior pharmacokinetic studies have measured tobramycin concentrations in CF sputum only by chemical means [immunoassay or highpressure liquid chromatography (HPLC)]. (3)(4)(5)12) In the current study, measurement of sputum tobramycin concentrations by bioassay (13) as well as HPLC allowed, for the first time, a comparison of bioactive and total tobramycin concentrations in respiratory secretions.…”

mentioning

confidence: 99%

“…Importantly, bioactive peak concentrations were generally well within the target concentration recommended by previous studies. In the original studies of tobramycin pharmacokinetics, (3,4) the target sputum concentration was 128 lg/g, 10-fold above the minimal inhibitory concentration (MIC) of 90% of Pa isolates at our institutions to account for sputum aminoglycoside inactivation. In the current study, 12 of 20 participants had a bioactive peak tobramycin concentration > 128 lg/g at both visits, with an additional four having a bioactive peak tobramycin concentration between 100 and 128 lg/g.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Sputum Tobramycin Concentrations in Cystic Fibrosis Patients with Repeated Administration of Inhaled Tobramycin

Ruddy

Emerson

Moss

et al. 2013

Journal of Aerosol Medicine and Pulmonary Drug Delivery

View full text Add to dashboard Cite

Background: Dosing of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF) patients was based on single-dose pharmacokinetic studies. This investigation was prompted by evidence of possible antibiotic accumulation in respiratory secretions with repeated dosing. The objectives were to evaluate whether tobramycin accumulates in respiratory secretions with repeated inhalation, compare total and biologically active tobramycin concentrations in CF sputum, and evaluate sputum induction for obtaining secretions for drug concentration assay. Methods: Individuals with CF ‡ 10 years of age were enrolled at the beginning of a course of TSI, 300 mg twice daily for 28 days. Two study visits were conducted, 1-2 days and 24-28 days after initiation of TSI treatment. Induced sputum and expectorated sputum samples were collected for measurement of trough and peak tobramycin concentrations at each visit. Total tobramycin concentrations were measured by high-pressure liquid chromatography and bioactive concentrations by bioassay. Results: Twenty participants completed the study. Trough concentrations were similar at visits 1 and 2, as were peak concentrations. Trough bioactive and total tobramycin concentrations were similar (mean ratio 1.2, 95% CI 0.56, 1.87), but peak bioactive concentrations were significantly lower than peak total concentrations (mean ratio 0.33, 95% CI 0.23, 0.44). Sputum induction was well tolerated. Conclusions: No evidence of significant drug accumulation in respiratory secretions with repeat dosing of TSI was seen. Peak bioactive concentrations, although lower than peak total concentrations, were still generally well within the bactericidal range. Sputum induction as a method for determining airway drug concentrations appears safe and feasible.

show abstract

mentioning

confidence: 84%

mentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Sputum Tobramycin Concentrations in Cystic Fibrosis Patients with Repeated Administration of Inhaled Tobramycin

Ruddy

Emerson

Moss

et al. 2013

Journal of Aerosol Medicine and Pulmonary Drug Delivery

View full text Add to dashboard Cite

show abstract

Effect of nebulizer type and antibiotic concentration on device performance

et al. 1997

View full text Add to dashboard Cite

We compared the performance of selected ultrasonic and jet nebulizers when aerosolizing several antibiotic formulations to determine optimum combinations for delivery of a respirable antibiotic aerosol. Three ultrasonic devices were tested: the UltraNeb 99/100®, the UltraAIR® and the Aerosonic®. The reusable jet nebulizers were the Dura ProNeb®, Pari‐LL® and the Sidestream®. The six disposable jet nebulizers were Marquest Acorn II®, Hudson T Updraft® II, Baxter MistyNeb®, Pari‐LC®, Pari IS‐2®, and a disposable Sidestream®. Each jet was tested with four compressors: a DeVilbiss AP‐50®, a Pulmo‐Aide®, a DuraNeb® and a PariMaster®. All nebulizing systems were initially tested with normal saline. From the initial data, six jet nebulizers and one ultrasonic device were tested with varying concentrations of tobramycin, gentamicin, ceftazidime, ciprofloxacin and colistin. Output was assessed by measuring volume (milliliters per minute), and amount of drug (milligrams per minute) nebulized. We then measured mean particle size of the antibiotic aerosol with seven jet nebulizers and two different compressors, Pulmo‐Aide® and PariMaster®, and two ultrasonic devices. The rate of nebulization of saline and antibiotic solutions (milliliters per minute) was greater with the ultrasonic device(s) than all jet nebulizer systems tested. Increasing the reservoir antibiotic concentration increased the drug output (milligrams per minute) with the jet nebulizers to a maximum, followed by decreasing output. When antibiotic concentrations were increased the output decreased more precipitously with the ultrasonic devices than with the jet nebulizers. At the highest antibiotic concentrations tested, the ultrasonic devices had the lowest output. Particle size distribution was most dependent on the specific jet device, with particle size distribution less affected by a specific antibiotic or its concentration. Higher reservoir concentrations can be utilized for increasing output of respirable antibiotic aerosols by jet nebulizers. We conclude that antibiotic output is dependent upon both the nebulizing system and the reservoir concentration of antibiotic. Pediatr Pulmonol. 1997; 23:249–260. © 1997 Wiley‐Liss, Inc.

show abstract