Primary objectiveTo establish whether saliva samples could be used as an alternative for blood samples in the therapeutic drug monitoring for amikacin and flucloxacillin. To meet this objective, a PK mod-el will be developed for amikacin and…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The concentration-time profile of saliva and plasma amikacin and flucloxacillin
levels in neonates.
Secondary outcome
The saliva-plasma ratio amikacin and flucloxacillin, pharmacokinetic
parameters, such as clearance (CL) and volume of distribution (Vd) will be
estimated from the data during model building, identification of covariates.
Background summary
Neonates are often admitted to the neonatology ward due to suspected infection.
In the Neth-erlands, amikacin and flucloxacillin are the antibiotics of choice
after 72h for the treatment of late-onset sepsis. Amikacin has a small
therapeutic index and therefore, therapeutic drug monitoring has to be
performed. This is done by taking two blood samples (peak and trough levels),
which causes a considerable burden for the neonate. TDM of flucloxacillin is
not (yet) performed on a routine basis. However, TDM of flucloxacillin is
considered when the therapy seems ineffective or it concerns an infection
caused by S. aureus, due to higher MIC*s. A non-invasive method of therapeutic
drug monitoring, for example in saliva, may be beneficial.
In the literature, little is known about the amikacin or flucloxacillin
concentrations in saliva. However, general principles of drug distribution
apply on to the salivary distribution of drugs. Both amikacin and
flucloxacillin have physicochemical properties that are favorable for the
distribution in saliva. Currently, a study is conducted in the AMC in which
saliva gentamicin (also a aminoglycoside) concentrations are monitored in
neonates. So far, the results from this study are promising (Mathôt, oral
communication).
This study aims to determine a correlation between saliva and plasma amikacin
and flucloxa-cillin concentrations in different neonatal subgroups. The
relationship between amikacin and flucloxacillin concentrations in plasma and
saliva will be described by a population PK model.
Study objective
Primary objective
To establish whether saliva samples could be used as an alternative for blood
samples in the therapeutic drug monitoring for amikacin and flucloxacillin. To
meet this objective, a PK mod-el will be developed for amikacin and
flucloxacillin saliva concentrations.
Secondary objective
To describe the relation between the saliva PK model and the plasma PK model.
Study design
Observational non-interventional study to establish the potential of measuring
amikacin and flucloxacillin saliva concentrations for the use of therapeutic
drug monitoring.
Study burden and risks
The peak- and through serum concentrations of amikacin and flucloxacillin are
determined according to clinical routine. No additional blood samples are
scheduled for this study.
The saliva samples are drawn using the SalivaBio Infant's Swab. These swabs are
designed specifically for the collection of saliva of young infants and can be
held during sampling, eliminating the risk of asphyxiation. The time-points of
saliva sampling are paired with clinical routine (i.e. before feeding), so the
infants are not disturbed more frequently when participating in this study.
The population that would benefit from the results from this study is highly
specific. Therefore, the subjects included in this study should be
representative for this study. A model derived from adults is unlikely to
predict amikacin and flucloxacillin levels in neonates, partly due to
differences in permeability of the salivary glands between these two age
groups. It TDM of saliva concentrations is found to be a valid alternative, it
will be no longer required to draw blood from neonates for TDM of amikacin and
flucloxacillin in the future.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. Treatment with amikacin and flucloxacillin i.v.
2. Signed informed consent from both parents or legal guardians, according to
local law and regulations
3. Admission to the neonatology ward, pediatrics/pediatric surgery department,
obstetrics department or maternity ward of the AMC
Exclusion criteria
1. Congenital disease of the salivary glands
2. Parent refusal
3. Inability to sample saliva
4. Inability to sample blood or monitor drug levels during treatment
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 | NL72011.018.19 |