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Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis
Author(s) -
Gibson Ronald L.,
RetschBogart George Z.,
Oermann Christopher,
Milla Carlos,
Pilewski Joseph,
Daines Cori,
Ahrens Richard,
Leon Kevin,
Cohen Morty,
McNamara Sharon,
Callahan Tracy L.,
Markus Richard,
Burns Jane L.
Publication year - 2006
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.20429
Subject(s) - aztreonam , medicine , sputum , cystic fibrosis , pharmacokinetics , inhalation , gastroenterology , tolerability , cmax , pharmacology , placebo , antibiotics , anesthesia , adverse effect , tuberculosis , microbiology and biotechnology , pathology , antibiotic resistance , alternative medicine , imipenem , biology
Background Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). Methods Pre‐clinical studies investigated the pre‐ and post‐nebulization activity of AI and its activity in the presence of CF sputum. A double‐blind, placebo‐controlled, dose‐escalation trial determined pharmacokinetics and tolerability of AI in subjects with CF. Single daily escalating doses of AI 75, 150, or 225 mg, or placebo were self‐administered using an eFlow® Electronic Nebulizer. Sputum samples were collected up to 4 hr and blood samples up to 8 hr post‐dose. Results AI activity against multiple CF isolates was retained after nebulization via eFlow, and activity was not inhibited by CF sputum. All 12 adult subjects and 11/12 adolescents tolerated all AI doses. One patient had an asymptomatic FEV 1 decrease >20% with the 150 mg dose. Median aztreonam sputum concentrations in adults 10 min after AI 75, 150, and 225 mg were 383, 879, and 985 µg/g, respectively. Median sputum concentrations in adolescents 10 min after AI 75, 150, and 225 mg were 324, 387, and 260 µg/g, respectively. Systemic exposure to AI was low. Plasma pharmacokinetics in adults receiving AI 75 mg were C max = 419 ng/g, T max = 0.99 hr, t 1/2 = 2.1 hr. Aztreonam concentrations in sputum were at or above the MIC 50 for at least 4 hr post‐dose. Conclusion These data support the continued development of AI for treatment of pulmonary infections in patients with CF. Pediatr Pulmonol. 2006; 41: 656–665. © 2006 Wiley‐Liss, Inc.