Gedrag van nasaal toegediende tobramycine en colistine in het lichaam van patiënten met taaislijmziekte

The sinonasal area of patients with Cystic Fibrosis (CF) can be a reservoir for P. aeruginosa from which cross-infection to the lungs may occur. Specific antimicrobial treatment for P. aeruginosa in the sinonasal area is not yet developed. Accurate treatment of this pathogen in the sinonasal area can prevent or postpone cross-infection to the lungs and consequently chronic lung infections. Studies of the pharmacokinetics of nasally administered tobramycin and colistin were never performed. Safety of this treatment has to be established before intervention studies on the effect of these drugs on clinical parameters are initiated. Systemic absorption can be used as surrogate parameter for safety.

Objective: To investigate the clinical pharmacokinetics of tobramycin and/or colistin after nasal administration.

Study design: Intervention study.

Study population: Patients of 18 or older with a confirmed diagnosis of Cystic Fibrosis attending the outpatient clinic of the Adult Cystic Fibrosis Center, Haga Teaching Hospital.

Intervention: Each patient irrigates the nose with tobramycin mixed with isotonic saline once, colistin dissolved in isotonic saline once and tobramycin and colistin together dissolved in isotonic saline once. Each subject visits the hospital six times. During three of those visits six venous blood samples are taken (in total 18 bloodsamples).

Bloodsamples are collected at: t = 0, 0.5, 1, 2, 4, 6 hours after the nasal lavage.

3 different types of nasal lavages: 1 = isotonic saline with tobramycin, 2 = isotonic saline with colistin, 3 = isotonic saline with tobramycin and colistin.
Each patient performs all three nasal lavages. No control group is necessary for this study. Patients perform each nasal lavage two times and for each nasal lavage the patient visits the hospital twice. The total duration of the study is 6 days.
For each type of nasal lavage 6 bloodsamples are taken, in which the concentration of the specific antibiotic is measured. With these data the farmacokinetics can be determined.