Journal Article

Safety and Pharmacokinetics of Ciprofloxacin Dry Powder for Inhalation in Cystic Fibrosis: A Phase I, Randomized, Single-Dose, Dose-Escalation Study

Staab, Doris, Delesen, Heinz, Stass, Heino, Nagelschmitz, Johannes

2015

Overview

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.

• Publisher: SAGE Publications,Mary Ann Liebert, Inc
• Subject: Administration, Inhalation / Adolescent / Adult / Anti-Bacterial Agents - administration & dosage / Anti-Bacterial Agents - adverse effects / Anti-Bacterial Agents - blood / Anti-Bacterial Agents - pharmacokinetics / Chemistry, Pharmaceutical / Ciprofloxacin - administration & dosage / Ciprofloxacin - adverse effects / Ciprofloxacin - blood / Ciprofloxacin - pharmacokinetics / Cystic Fibrosis - blood / Cystic Fibrosis - drug therapy / Cystic Fibrosis - microbiology / Cystic Fibrosis - physiopathology / Dry Powder Inhalers / Female / Germany / Humans / Lung - drug effects / Lung - microbiology / Lung - physiopathology / Male / Powders / Pseudomonas aeruginosa - drug effects / Pseudomonas aeruginosa - pathogenicity / Pseudomonas Infections - drug therapy / Pseudomonas Infections - microbiology / Pseudomonas Infections - physiopathology / Respiratory Tract Infections - drug therapy / Respiratory Tract Infections - microbiology / Respiratory Tract Infections - physiopathology / Single-Blind Method / Sputum - metabolism / Treatment Outcome / Young Adult