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Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety.
Pediatr Pulmonol. 2007 Apr; 42(4):307-13.PP

Abstract

Aerosolized antibiotics are associated with a high treatment burden that can result in non-adherence to chronic therapy. We evaluated the pharmacokinetics (PK) and safety of tobramycin inhalation powder (TIP), a novel dry-powder formulation designed to deliver a high payload of tobramycin topically to the lungs for management of chronic Pseudomonas aeruginosa infections. This was a multi-center, open-label, sequential-cohort, single-dose, dose-escalation study using the standard 300 mg dose of tobramycin solution for inhalation (TSI) as an active control. Subjects were randomized to TIP or TSI in a 3:1 ratio in each of five cohorts. Measurements included serum and sputum tobramycin concentrations, administration time, serum chemistries, acute change in lung function, and adverse events (AEs). Out of 90 randomized subjects, 86 had data for safety analysis; and 84 had data for PK analysis. Serum tobramycin PK profiles were similar for TIP and TSI. Four capsules of 28 mg TIP (total tobramycin dose 112 mg) produced comparable systemic exposure to 300 mg TSI, in less than one-third the administration time. The most common AEs associated with TIP were cough (20%) and dysgeusia (17%). TIP allows for faster and more efficient pulmonary delivery of tobramycin than TSI and has a safety profile that supports continued clinical investigation. The increased rate of local respiratory tract irritation noted with TIP is not unexpected with a high-payload powder formulation. The development of dry powder inhaled antibiotics may represent an important advance in the treatment of chronic lung infections.

Authors+Show Affiliations

Nemours Children's Clinic, Orlando, Florida 32806, USA. dgeller@nemours.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17352404

Citation

Geller, David E., et al. "Novel Tobramycin Inhalation Powder in Cystic Fibrosis Subjects: Pharmacokinetics and Safety." Pediatric Pulmonology, vol. 42, no. 4, 2007, pp. 307-13.
Geller DE, Konstan MW, Smith J, et al. Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. Pediatr Pulmonol. 2007;42(4):307-13.
Geller, D. E., Konstan, M. W., Smith, J., Noonberg, S. B., & Conrad, C. (2007). Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. Pediatric Pulmonology, 42(4), 307-13.
Geller DE, et al. Novel Tobramycin Inhalation Powder in Cystic Fibrosis Subjects: Pharmacokinetics and Safety. Pediatr Pulmonol. 2007;42(4):307-13. PubMed PMID: 17352404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. AU - Geller,David E, AU - Konstan,Michael W, AU - Smith,Jeffrey, AU - Noonberg,Sarah B, AU - Conrad,Carol, PY - 2007/3/14/pubmed PY - 2007/6/20/medline PY - 2007/3/14/entrez SP - 307 EP - 13 JF - Pediatric pulmonology JO - Pediatr Pulmonol VL - 42 IS - 4 N2 - Aerosolized antibiotics are associated with a high treatment burden that can result in non-adherence to chronic therapy. We evaluated the pharmacokinetics (PK) and safety of tobramycin inhalation powder (TIP), a novel dry-powder formulation designed to deliver a high payload of tobramycin topically to the lungs for management of chronic Pseudomonas aeruginosa infections. This was a multi-center, open-label, sequential-cohort, single-dose, dose-escalation study using the standard 300 mg dose of tobramycin solution for inhalation (TSI) as an active control. Subjects were randomized to TIP or TSI in a 3:1 ratio in each of five cohorts. Measurements included serum and sputum tobramycin concentrations, administration time, serum chemistries, acute change in lung function, and adverse events (AEs). Out of 90 randomized subjects, 86 had data for safety analysis; and 84 had data for PK analysis. Serum tobramycin PK profiles were similar for TIP and TSI. Four capsules of 28 mg TIP (total tobramycin dose 112 mg) produced comparable systemic exposure to 300 mg TSI, in less than one-third the administration time. The most common AEs associated with TIP were cough (20%) and dysgeusia (17%). TIP allows for faster and more efficient pulmonary delivery of tobramycin than TSI and has a safety profile that supports continued clinical investigation. The increased rate of local respiratory tract irritation noted with TIP is not unexpected with a high-payload powder formulation. The development of dry powder inhaled antibiotics may represent an important advance in the treatment of chronic lung infections. SN - 8755-6863 UR - https://www.unboundmedicine.com/medline/citation/17352404/Novel_tobramycin_inhalation_powder_in_cystic_fibrosis_subjects:_pharmacokinetics_and_safety_ L2 - https://doi.org/10.1002/ppul.20594 DB - PRIME DP - Unbound Medicine ER -