Population pharmacokinetics of cefazolin in maternal and umbilical cord plasma, and simulated exposure in term neonates.
J Antimicrob Chemother
; 76(12): 3229-3236, 2021 11 12.
Article
en En
| MEDLINE
| ID: mdl-34499720
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cefazolina
/
Antibacterianos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Newborn
/
Pregnancy
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2021
Tipo del documento:
Article
País de afiliación:
Bélgica