Development and prospective validation of a pharmacokinetic model of flucloxacillin for dosing in patients with impaired renal function.
ID
Source
Brief title
Condition
- Other condition
- Bacterial infectious disorders
Synonym
Health condition
Nierfunctiestoornissen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study endpoint is the development of a PK-model for dosing of
flucloxacillin in patients with impaired renal function.
Secondary outcome
Secondary endpoint is the predictive value of the model for dosing of
flucloxacillin in patients with impaired renal function.
Background summary
So far, only one study described the disposition of flucloxacillin and its
active metabolite 5-hydroxyflucloxacillin in patients with impaired renal
function. This study was conducted by Thijssen and colleagues and included only
5 patients with creatinine clearances ranging from 10-15 ml/min. Although the
study demonstrated a reduction in renal clearance, higher peak concentrations
and accumulation of the active metabolite 5-hydroxyflucloxacillin, the authors
concluded that dose adjustment is not necessary because of the low toxic
potential of penicillins. Based on the results of this single preliminary
study, dose adjustment for flucloxacillin is not recommended by the Royal Dutch
Pharmacists Association (KNMP) in patients with impaired renal function (eGFR
>10 ml/min). However, the SPC warns that high intravenous doses of
flucloxacillin in patients with impaired renal function are associated with
neurological abnormalities like convulsions. This has also been reported
several times in hospitals in The Hague where continuous infusion of
flucloxacillin in patients with impaired renal function resulted in high plasma
concentrations of flucloxacillin (>100 mg/l) and were associated with the
occurrence of convulsions. This indicates that dose adjustment might be
necessary in patients with impaired renal function. Therefore, more information
is needed on dosing of flucloxacillin in case of impaired renal function.
Presumed is that a pharmacokinetic model will lead to better individual dosing
of flucloxacillin, especially in patients with impaired renal function.
Study objective
Development and prospective validation of a pharmacokinetic model of
flucloxacillin for dosing in patients with impaired renal function.
Study design
This study includes PK-modeling. Based on retrospective data from colleagues in
The Hague an initial pharmacokinetic model will be developed. This model will
be validated with Monte Carlo simulation and confirmed using new data from
patients included in a clinical trial. For these patients a prediction will be
done what the expected plasmaconcentration will be at a defined moment, based
on the patients properties like body weight, age, renal function. At this time
point a plasma sample will be drawn and the measured concentration will be
compared with the predicted concentration. De difference between the two levels
is an indication of the precision of the model. The difference should be less
than 20%.
Study burden and risks
Not applicable.
Henri Dunantstraat 5
Heerlen 6419PC
NL
Henri Dunantstraat 5
Heerlen 6419PC
NL
Listed location countries
Age
Inclusion criteria
- adults treated with oral or intravenous flucloxacillin
- normal and impaired renal function expressed as MDRD and corrected for BSA (body surface area)
Exclusion criteria
- patients younger than 18 years of age;
- legally incapable patients;
- contra-indication or allergy to the treatment with flucloxacillin;
- pregnant patients;
- patients receiving dialysis.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL48078.096.14 |