Affiliation:
1. Pharmacy and Clinical Pharmacology Amsterdam UMC location University of Amsterdam Meibergdreef 9 Amsterdam The Netherlands
2. Amsterdam UMC location University of Amsterdam Neonatology, Meibergdreef 9 Amsterdam The Netherlands
Abstract
Amikacin is an aminoglycoside antibiotic that is frequently used for the treatment of neonatal late‐onset sepsis, for which therapeutic drug monitoring (TDM) is advised. In order to decrease the TDM associated burden of plasma sampling, a noninvasive TDM method using saliva samples was investigated.MethodsThis was a prospective single‐centre, observational feasibility study with 23 premature and term neonates from whom up to 8 saliva samples were collected, together with residual plasma from clinical routine. Amikacin concentrations in saliva and plasma were quantified with liquid chromatography–tandem mass spectrometry. A population pharmacokinetic analysis was performed to develop an integrated pharmacokinetic model of amikacin in plasma and saliva and for the identification of covariates. TDM performance of different sampling regimens was evaluated using Monte Carlo simulations in a fictional cohort of representative neonates (n = 10 000).ResultsAmikacin could be detected in saliva and a saliva compartment was appended to a 2‐compartment plasma model. First‐order absorption (k13) of the saliva compartment was 0.0345 h−1 with an interindividual variability of 45.3%. The rate of first‐order elimination (k30) was 0.176 h−1. Postmenstrual age had a significant negative covariate effect on k13, with an exponent of −4.3. Target attainment increased from 77.6 to 79.2% and from 79.9 to 83.2% using 1–to 5 saliva samples or 1–5 plasma samples, respectively.ConclusionTDM of amikacin using saliva samples results in target attainment comparable to plasma samples and may be beneficial for (premature) neonates with late‐onset sepsis.
Funder
Janivo Stichting
Amsterdam University Medical Centers
Subject
Pharmacology (medical),Pharmacology