Fornari, C; Arrieta, A; Bradley, JS; Tout, M; Magalhaes, P; Auriol, FK; Borella, E; ... Habboubi, N; + view all Fornari, C; Arrieta, A; Bradley, JS; Tout, M; Magalhaes, P; Auriol, FK; Borella, E; Piana, C; Pasqua, OD; Vallespir, BP; Mazzei, P; Bokesch, PM; Hoover, R; Capriati, A; Habboubi, N; - view fewer (2024) Dose rationale for the use of meropenem/vaborbactam combination in paediatric patients with Gram-negative bacterial infections. British Journal of Clinical Pharmacology 10.1111/bcp.16145. (In press).

	Text (Article) Della Pasqua_Vaborem PKPD_paediatrics_Manuscript_Final_for post-acceptance.pdf Access restricted to UCL open access staff until 27 June 2025. Download (691kB)
	Text (Figure 1) Della Pasqua_Figure_1.pdf Access restricted to UCL open access staff until 27 June 2025. Download (83kB)
	Text Della Pasqua_Figure_2.pdf Access restricted to UCL open access staff until 27 June 2025. Download (137kB)
	Text (Figure 3) Della Pasqua_Figure_3.pdf Access restricted to UCL open access staff until 27 June 2025. Download (508kB)
	Text (Figure 4) Della Pasqua_Figure_4.pdf Access restricted to UCL open access staff until 27 June 2025. Download (134kB)

Abstract

Aims: Meropenem/vaborbactam combination is approved in adults by FDA and EMA for complicated urinary tract infections and by EMA also for other Gram-negative infections. We aimed to characterise the pharmacokinetics of both moieties in an ongoing study in children and use a model-based approach to inform adequate dosing regimens in paediatric patients. / Methods: Over 4196 blood samples of meropenem and vaborbactam (n = 414 subjects) in adults, together with 114 blood samples (n = 39) in paediatric patients aged 3 months to 18 years were available for this analysis. Data were analysed using a population with prior information from a pharmacokinetic model in adults to inform parameter estimation in children. Simulations were performed to assess the suitability of different dosing regimens to achieve adequate probability of target attainment (PTA). / Results: Meropenem/vaborbactam PK was described with two-compartment models with first-order elimination. Body weight and CLcr were significant covariates on the disposition of both drugs. A maturation function was evaluated to explore changes in clearance in neonates. PTA ≥90% was derived for children aged ≥3 months after 3.5-h IV infusion of 40 mg/kg Q8h of both meropenem and vaborbactam and 2 g/2 g for those ≥50 kg. Extrapolation of disposition parameters suggest that adequate PTA is achieved after a 3.5-h IV infusion of 20 mg/kg for neonates and infants (3 months). / Conclusions: An integrated analysis of adult and paediatric data allowed accurate description of sparsely sampled meropenem/vaborbactam PK in paediatric patients and provided recommendations for the dosing in neonates and infants (3 months).

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as XMLJSONCSV

Archive Staff Only

View Item