| Autor: |
Keij, FM, Kornelisse, RF, Hartwig, NG, van der Sluijs, J, van Driel, A, Kenter, S, Heidema, J, den Butter, P, Koch, BCP, Reiss, IKM, Allegaert, K, Tramper-Stranders, GA |
| Zdroj: |
Archives of Disease in Childhood; 2019, Vol. 104 Issue: 6 pe37-e37, 1p |
| Abstrakt: |
BackgroundClavulanic acid is an irreversible beta-lactamase inhibitor which has a weak antibacterial action. When combined with a beta-lactam antibiotic such as amoxicillin, it is effective against a broad range of bacteria. Despite its widespread use, little is known on the mechanism of action and target levels. A few studies on oral clavulanic acid in adults are available reporting great variance (AUC median 4.99 mg·h/L [0.44–8.31])1and a short elimination half-time (1.08h).2Observations in neonates are currently lacking. We therefore evaluated the pharmacokinetics of oral clavulanic acid co-administered with amoxicillin in term newborns.MethodsAs part of a multicenter RCT (Clinicaltrials.gov:NCT03247920) evaluating neonatal intravenous-to-oral switch therapy in probable bacterial infection, we measured serum levels in patients allocated to the intervention group. They switched to amoxicillin/clavulanic acid suspension (25/6.25 mg/kg tid), after 48 hours of intravenous penicillin/gentamicin. Two blood samples from different dosing intervals, were obtained and directly stored at -80°C. Initially, and to ensure that amoxicillin levels were attained as safety marker, levels in the second part of the timeframe (4–8 h after administration) were collected. For the second batch, peak levels (1–2 h after administration) were collected. Analysis was performed using Liquid Chromatography and Mass Spectrometry.ResultsAt submission, samples of the first 15 patients were analysed (first batch). Samples were collected 6.0 ± 1.3 h (mean,S.D.) after antibiotic administration. Clavulanic acid levels were detected in all patients but a great variance was observed (median: 1.4 mg/L; range: 0.20–4.82 mg/L). Extrapolation would lead to an AUC of at least 8.4 mg·h/L.ConclusionsOral clavulanic acid is absorbed in term newborns, but great variance is seen in trough levels (4–8 h after administration). Extrapolation predicts at least an AUC comparable to those of adults. Peak levels in the first part of the time interval (0–4h) are needed to further build confidence on this conclusion.ReferencesDe Velde F, De Winter BCM, Koch BCP, Van Gelder T, Mouton JW, Consortium C-N. Highly variable absorption of clavulanic acid during the day: a population pharmacokinetic analysis. J Antimicrob Chemother. 2018;73(2):469–76.Vree TB, Dammers E, Exler PS. Identical pattern of highly variable absorption of clavulanic acid from four different oral formulations of co-amoxiclav in healthy subjects. J Antimicrob Chemother2003;51(2):373–8.Disclosure(s)Nothing to disclose |
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