Bioavailability of oral ciprofloxacin tablets versus suspension in pediatric cancer patients

Ciprofloxacin is an antibiotic drug which is routinely used as anti-microbial
prophylaxis during the treatment of pediatric cancer patients. Both tablets and
oral suspension are used interchangeably without altering the dose. However
bioavailability and therefore exposure might differ between these formulations.
Bioavailability should be determined in the target population. Current studies
show conflicting results and these data should not be extrapolated to our
target population, due to essential differences between the healthy adult
volunteers and children with cancer. With this study we are one step closer to
individual dosing.

To determine the relative bioavailability of ciprofloxacin oral suspension
versus oral tablets in pediatric cancer patients, and to determine the absolute
bioavailability of tablets and suspension utilizing the 100% bioavailability of
intravenous administration. This will enable correct dose adjustments when
switching between the different formulations. The results will be incorporated
in a large ciprofloxacin PKPD study (METC 2012-287).

This is an open label randomized cross-over pharmacokinetic study in children
using ciprofloxacin according to standard treatment guidelines.

Patients will be randomized to determine the starting formulation. The total
treatment study period is 14 days; subjects will start with 7 days of oral
solution and thereafter switched to 7 days of tablets or vice versa. During the
treatment with each formulation 6 blood samples will be taken at least 48 hours
after start of treatment (samples at steady state). In total 18 samples will be
taken (6 per formulation).

We will perform this study in the target population, as children will receive
this medication as part of standard treatment, and the burden is minor given
that blood sampling (6 steady state blood samples per administration route)
will be done using the central line in place for chemotherapeutic treatment.
The only intervention is the different formulations that will be used. There
will be no washout, hence no interruption of standard treatment. Visits will be
combined as much as possible with regular visits to the day care or the
outpatient clinic or when patients are hospitalized for chemotherapy.
The patient is not allowed to take a heavy meal one hour prior to and one hour
after administration of study medication.