[en] Background:Intra-partum cefazolin is used to prevent group BStreptococcus(GBS) vertical transmission inmothers allergic to penicillin without a history of anaphylaxis.Objectives:To investigate the maternal cefazolin dose–exposure relationship and subsequent maternal andneonatal target attainment at delivery.Methods:Data were obtained from 24 healthy, GBS-colonized pregnant women (20–41 years), undergoing vagi-nal delivery (gestational age 37 weeks). During labour, all women received a 2 g cefazolin IV infusion. Eighthours later, eight women received another 1 g in the event of delayed (>8 h) delivery. Next to maternal plasmaconcentrations (up to 10 per dosing interval, until delivery), venous and arterial umbilical cord concentrationswere determined at delivery. Target attainment in maternal/neonatal plasma was set at 1 mg/L for 60% of thedosing interval (unbound cefazolin, worst-case clinical breakpoint). A population pharmacokinetic (popPK) modelwas built (NONMEM 7.4). ClinicalTrials.gov Identifier: NCT01295606.Results:At delivery, maternal blood and arterial umbilical cord unbound cefazolin concentrations were >1 mg/Lin 23/24 (95.8%) and 11/12 (91.7%), respectively. The popPK of cefazolin in pregnant women was described by atwo-compartment model with first-order elimination. Two additional compartments described the venous andarterial 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 showedadequate maternal and umbilical cord exposure for 12 h following the first dose.Conclusions:PopPK simulations showed that standard pre-delivery maternal cefazolin dosing providedadequate target attainment up to the time of delivery.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Elkayal, Omar
Allegaert, Karel
Spriet, Isabel
Smits, Anne
SEGHAYE, Marie-Christine ; Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
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