title: Safety and pharmacokinetics of ciprofloxacin dry powder for inhalation in cystic fibrosis: a phase I, randomized, single-dose, dose-escalation study.
abstract: BACKGROUND
  Reliable, reproducible deposition to the lung is a major prerequisite for the clinical use of inhaled drugs. Ciprofloxacin dry powder for inhalation (ciprofloxacin DPI; Bayer HealthCare AG, Leverkusen, Germany) is an antibacterial therapy in development using Novartis' PulmoSphere™ technology (Novartis Pharma AG, Basel, Switzerland) for the targeted delivery of ciprofloxacin to the lung via a T-326 inhaler.
  
  
  METHODS
  This randomized, single-blind, placebo-controlled, dose-escalation study investigated the safety, tolerability, and pharmacokinetics of single-dose ciprofloxacin DPI (32.5 mg [n=6] or 65 mg [n=6]) and matching placebo (n=4) in adult patients with cystic fibrosis and stable pulmonary status (forced expiratory volume in 1 sec ≥30%) who were colonized with Pseudomonas aeruginosa.
  
  
  RESULTS
  Peak sputum concentrations of 34.9 mg/L (range 2.03-229) and 376 mg/L (8.95-1283) for ciprofloxacin 32.5 mg and 65 mg, respectively, indicated targeting of ciprofloxacin DPI to the lung. This contrasted with low systemic exposure (peak plasma concentrations: 0.0790 mg/L [32.5 mg] and 0.182 mg/L [65 mg]). Single-dose ciprofloxacin DPI 32.5 mg or 65 mg was well tolerated with similar incidences of adverse events across all groups. No deaths, discontinuations, treatment-related serious adverse events, or clinically relevant changes in laboratory parameters, vital signs, or lung function tests were reported.
  
  
  CONCLUSIONS
  Lung targeting with high pulmonary concentrations of ciprofloxacin combined with low systemic exposure was confirmed. These results support further study of ciprofloxacin DPI as a potentially more convenient alternative to nebulized antibiotic solutions for managing chronic lung infections.
authors: 1 Bayer Pharma AG, Global Drug Discovery, Development Clinical Pharmacology, Cardiovascular/Primary Care, Bayer Pharma AG , D-42113, Wuppertal, Germany .
authors: Heino
authors: H
authors: Stass
authors: Heinz
authors: H
authors: Delesen
authors: Johannes
authors: J
authors: Nagelschmitz
authors: Doris
authors: D
authors: Staab
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D058995:Dry Powder Inhalers; D005260:Female; D005858:Germany; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D011208:Powders; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D016037:Single-Blind Method; D013183:Sputum / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D011208:Powders; D002939:Ciprofloxacin
keywords: Ciprofloxacin DPI; Cystic fibrosis; Pseudomonas aeruginosa; long-term treatment; lung targeting