Pharmacokinetics of inhaled colistin in patients with cystic fibrosis

• Published in: Journal of antimicrobial chemotherapy 2006-02, Vol.57 (2), p.306-311
• Main Authors: Ratjen, F., Rietschel, E., Kasel, D., Schwiertz, R., Starke, K., Beier, H., van Koningsbruggen, S., Grasemann, H.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adult; airways; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; antimicrobial therapy; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Colistin - administration & dosage; Colistin - pharmacokinetics; Cystic Fibrosis - metabolism; Errors of metabolism; Female; Forced Expiratory Volume - physiology; Humans; Male; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous hereditary metabolic disorders; Nebulizers and Vaporizers; Pharmacology. Drug treatments; Pseudomonas; Pseudomonas aeruginosa; Sputum - metabolism
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dki461

Objectives: Inhaled colistin is commonly used in patients with cystic fibrosis (CF), but only limited data are available to define its pharmacokinetic profile. Patients and methods: We performed a multicentre study in 30 CF patients to assess sputum, serum and urine concentrations after a single dose of 2 million units of colistin administered by inhalation. In a subgroup of patients we also compared the efficacy of two different nebulizers for administration of inhaled colistin. Results: Serum concentrations of colistin reached their maximum 1.5 h after inhalation and decreased thereafter. Serum concentrations were well below those previously reported for systemic application in all patients. A mean 4.3 ± 1.3% of the inhaled dose was detected in urine. Elimination characteristics did not differ significantly from those previously reported for systemic application. A positive correlation was found between forced expiratory volume in 1 s (FEV1) in per cent predicted and both AUC and maximal colistin concentrations in serum (Cmax). Maximum sputum concentrations were at least 10 times higher than the MIC breakpoint for Pseudomonas aeruginosa proposed by the British Society for Antimicrobial Chemotherapy. Although sputum drug concentrations decreased after a peak at 1 h, the mean colistin concentrations were still above 4 mg/L after 12 h. No differences were seen in polymyxin E sputum concentrations, for CF patients between the two nebulizer systems. Conclusions: The low systemic and high local concentrations of colistin support the use of inhaled colistin in CF patients infected with P. aeruginosa.