Dry powder inhalation of colistin in cystic fibrosis patients: a single dose pilot study.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Westerman
E M
EM
Apotheek Haagse Ziekenhuizen, P.O. Box 43100, 2504 AC The Hague, The Netherlands. e.westerman@ahz.nl
De Boer
A H
AH
Le Brun
P P H
PP
Touw
D J
DJ
Roldaan
A C
AC
Frijlink
H W
HW
Heijerman
H G M
HG
D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003091:Colistin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005540:Forced Expiratory Flow Rates / Q000187:drug effects; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D011208:Powders; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D011208:Powders; D003091:Colistin