Pharmacokinetics of nasally administered tobramycin and colistin in Cystic Fibrosis

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. At present
adequate inhalation therapy with antibiotics for P. aeruginosa in the lungs is
available. However, 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. This is the
first study to investigate the clinical pharmacokinetics of these drugs. 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.

To investigate the clinical pharmacokinetics of tobramycin and/or colistin
after nasal administration. With this pharmacokinetic parameters the safety of
this treatment can be investigated.

Intervention study.

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. In between these three
administrations a minimum of 2 days is required.

Each subject visits the hospital six times. During three of those visits six
venous blood samples are taken (in total 18 bloodsamples). Adverse events and
serious adverse events will be closely monitored. Possible discomfort
associated with nasally administered tobramycin and/or colistin could be local
irritation, burning sensation in the nose, throat irritation and nose bleeds.
Patients with Cystic Fibrosis could benefit from antimicrobial treatment of the
sinonasal area. However, first safety of this treatment has to be established
before clinical intervention studies are initiated. Due to CF-specific
characteristics these pharmacokinetic models should be tested on patients with
CF.