Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: A pilot study

Central Hospital Pharmacy The Hague, The Hague, The Netherlands.
Journal of Cystic Fibrosis (Impact Factor: 3.48). 03/2004; 3(1):23-8. DOI: 10.1016/j.jcf.2003.12.005
Source: PubMed


Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin. However, nebulized colistin can cause bronchoconstriction in CF patients. Therefore, in the progress of developing a dry powder formula, the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects. To investigate the side effects, a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF-patients.
Nine CF-patients chronically infected with P. aeruginosa participated in a double blind, randomized cross over study. On two visits to the outpatient clinic, patients were submitted to either nebulized colistin sulphate or colistin sulphomethate solution. Lung function tests were performed immediately before and 15 and 30 min after nebulization.
Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate. A significant decrease in mean changes (SD) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3% (8.6%), -5.7% (7.3%) and -8.4% (7.5%) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate (P < 0.05). Seven patients were not able to complete the nebulization of colistin sulphate because of throat irritation and severe cough.
Based on these results it was concluded that inhalation with nebulized colistin sulphate is not suitable for treatment of CF patients chronically infected with P. aeruginosa. Colistin sulphomethate is the drug of choice for pulmonary administration of colistin.

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    • "Although the dry powder inhalation was appreciated by the patients, some experienced serious cough as adverse effect. This appeared to be a result of the chemical structure of the colistin sulfate salt and it was concluded that colistimethate sodium, which is currently used by many CF patients by nebulisation, is the colistin salt of choice for further development of a dry powder inhaler (Westerman et al., 2004). Serum concentration results from the study by Le Brun (Le Brun et al., 2002) and the current study should be compared with caution, as data obtained in the Le Brun study are retrieved from a different dry powder inhaler and from both colistin sulfate (DPI) and colistimethate sodium (nebulisation) administration, while only colistimethate sodium was used in the current study. "
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    ABSTRACT: Dry powder inhalation (DPI) may be an alternative to nebulisation of drugs in the treatment of chest infections in cystic fibrosis (CF) patients. In a pilot study the feasibility of a colistin dry powder inhaler (prototype Twincer) by a single dose in CF-patients was assessed and compared to nebulised colistin. Ten CF-patients, chronically infected with P. aeruginosa, participated in a randomised cross over study. On two visits to the outpatient clinic, patients inhaled colistin sulphomethate as 25 mg dry powder (Twincer) or as 158 mg nebulised solution (Ventstream nebuliser, PortaNeb compressor). Pulmonary function tests were performed before, 5 and 30 min after inhalation. Serum samples were drawn prior to each dose and at 15, 45 min, 1.5; 2.5; 3.5 and 5.5 h after inhalation. The DPI was well tolerated by the patients: no significant reduction in FEV1 was observed. Relative bioavailability of DPI to nebulisation was approx. 140% based on actual dose and approx. 270% based on drug dose label claim. The colistin DPI (Twincer inhaler) is well tolerated and appreciated by CF-patients. Optimisation with respect to particle size and internal resistance of the inhaler is necessary to attain equivalent pulmonary deposition to liquid nebulisation.
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    • "Inhalation doses of 1–2 million units (approximately 80 to 160 mg) of colistin methanesulphonate per day are recommended. The methanesulphonate is preferred as colistin sulphate inhalation has a high incidence of respiratory irritation [133]. The value of this approach for the prevention or delay of the onset of chronic colonization with P. aeruginosa and its associated effects on deterioration in lung function has been confirmed [17]. "
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