Defining the optimal dose for continuous flucloxacillin infusion using pharmacokinetic modelling ;The FLUCON-study

The small spectrum antibiotic flucloxacillin is approved in an intermittent
dosing regime. The antibacterial activity of flucloxacillin is time dependent
so continuous infusion is probably more effective. Furthermore, for some
patients continuous dosing can have practical benefits. As it stands, the
optimal flucloxacillin dosage for continuous infusion is unknown. Studies
indicate that a lower dosage of continuous infusion might be sufficient.

Step 1
Primary objective: To describe the population pharmacokinetics of
flucloxacillin for non-critically ill patients and determine the influence of
covariates (demographics and renal function) on the kinetics of flucloxacillin.

Step 2
Primary objective: To determine the continuous dosing scheme of flucloxacillin
to obtain a pharmacokinetic target of 100% fT>MIC (with a maximum unbound
flucloxacillin concentration of 7,5mg/L) for 90% of the population.

Step 3
Primary objective: To validate the new continuous dosing scheme of
flucloxacillin on the pharmacokinetic endpoint of 100% fT>MIC (with a maximum
unbound flucloxacillin concentration of 7,5mg/L) for 90% of the population.

Part A: multi centre, cross-sectional non-randomized observational study in 30
patients. On two separate days flucloxacillin levels are measured.
Part B: multi centre, non-randomized interventional study. Patients will
receive the new continuous dosing scheme and therapeutic drug monitoring (TDM)
will be conducted.

Part B: Patients will receive the new dosing scheme for continuous
flucloxacillin therapy and TDM will be conducted.

Flucloxacillin is a registered product and used within the indication and not
in combination with other products.
The remaining risks for the subjects participating in the study are acceptable
since part A involves mainly standard care. Only additional blood samples are
taken, which has a low risk for complications. In general the risk for
participation in this study is regarded low. The risk of suboptimal dosing in
part B is minimized by performing therapeutic drug monitoring as soon as
possible. Suboptimal dosages will be detected soon and dose adjustments can be
made.
Benefits for patients participating in part A will be that they will receive
information on the optimal dosage of flucloxacillin, when administrated as a
continuous infusion. Participants in part B might experience less side effects.