Bioavailability of oral ciprofloxacin tablets versus suspension in pediatric cancer patients

Rationale: 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.



Objective: 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.



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



Study population: 15 pediatric cancer patients in the range of 1-19 years, who are treated with ciprofloxacin prophylaxis as part of standard treatment.



Intervention: Patients receiving ciprofloxacin for antibiotic prophylaxis during chemotherapy treatment according to standard supportive care guidelines will be randomized to receive either ciprofloxacin tablets or oral suspension (50 mg/ml) for 7 consecutive days, and subsequently switch to the other formulation for the following 7 days, without a washout period in between. One random oral dose will be replaced by an intravenous dose of ciprofloxacin to determine the absolute bioavailability. During this period, blood samples will be drawn from the available Portacath catheter.



Main study parameters/endpoints: Determination of bioavailability (F), and related parameters: Tmax,ss, Cmax,ss, AUC.

*NTR4047 ended because of too low number of inclusions (=2).

Whether the bioavailability of ciprofloxacin oral suspension and tablets are equivalent and can therefore be used interchangeably.

Three sampling days (one for each formulation).

Sampling day: trough level, ciprofloxacin intake, 0,5h, 1h, 1,5h, 2h, and 6h.

Patients are treated with ciprofloxacin as standard treatment. However for this study, ciprofloxacin will be relabeled as study medication for the duration of the study. 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. Patients will be randomized to determine the starting formulation. 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).