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Population pharmacokinetics of cefazolin in maternal and umbilical cord plasma, and simulated exposure in term neonates

Tijdschriftbijdrage - Tijdschriftartikel

BACKGROUND: Intra-partum cefazolin is used to prevent group B Streptococcus (GBS) vertical transmission in mothers allergic to penicillin without a history of anaphylaxis. OBJECTIVES: To investigate the maternal cefazolin dose-exposure relationship and subsequent maternal and neonatal target attainment at delivery. METHODS: Data were obtained from 24 healthy, GBS-colonized pregnant women (20-41 years), undergoing vaginal delivery (gestational age ≥37 weeks). During labour, all women received a 2 g cefazolin IV infusion. Eight hours later, eight women received another 1 g in the event of delayed (>8 h) delivery. Next to maternal plasma concentrations (up to 10 per dosing interval, until delivery), venous and arterial umbilical cord concentrations were determined at delivery. Target attainment in maternal/neonatal plasma was set at 1 mg/L for 60% of the dosing interval (unbound cefazolin, worst-case clinical breakpoint). A population pharmacokinetic (popPK) model was built (NONMEM 7.4). ClinicalTrials.gov Identifier: NCT01295606. RESULTS: At delivery, maternal blood and arterial umbilical cord unbound cefazolin concentrations were >1 mg/L in 23/24 (95.8%) and 11/12 (91.7%), respectively. The popPK of cefazolin in pregnant women was described by a two-compartment model with first-order elimination. Two additional compartments described the venous and arterial umbilical cord concentration data. Cefazolin target attainment was adequate in the studied cohort, where delivery occurred no later than 6.5 h after either the first or the second dose. PopPK simulations showed adequate maternal and umbilical cord exposure for 12 h following the first dose. CONCLUSIONS: PopPK simulations showed that standard pre-delivery maternal cefazolin dosing provided adequate target attainment up to the time of delivery.
Tijdschrift: Journal of Antimicrobial Chemotherapy
ISSN: 0305-7453
Issue: 12
Volume: 76
Pagina's: 3229 - 3236
Aantal pagina's: 8
Jaar van publicatie:2021
Trefwoorden:Parageneeskundige wetenschappen , Farmacologie en toxicologie, Microbiologie