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

Elkayal, Omar (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.
Allegaert, Karel (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;Katholieke Univ Leuven, Dept Dev & Regenerat, Leuven, Belgium.;Erasmus MC, Dept Clin Pharm, Rotterdam, Netherlands.
Spriet, Isabel (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
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Smits, Anne (författare)
Katholieke Univ Leuven, Dept Dev & Regenerat, Leuven, Belgium.;Univ Hosp Leuven, Neonatal Intens Care Unit, Leuven, Belgium.
Seghaye, Marie-Christine (författare)
Ctr Hosp Univ Liege, Dept Paediat, Liege, Belgium.
Charlier, Corinne (författare)
Ctr Hosp Univ Liege, Dept Toxicol, Liege, Belgium.
Dreesen, Erwin (författare)
Uppsala universitet,Institutionen för farmaci,Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium
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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;Katholieke Univ Leuven, Dept Dev & Regenerat, Leuven, Belgium.;Erasmus MC, Dept Clin Pharm, Rotterdam, Netherlands. (creator_code:org_t)
Oxford University Press (OUP), 2021
2021
Engelska.
Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 76:12, s. 3229-3236
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • BackgroundIntra-partum cefazolin is used to prevent group B Streptococcus (GBS) vertical transmission in mothers allergic to penicillin without a history of anaphylaxis.ObjectivesTo investigate the maternal cefazolin dose–exposure relationship and subsequent maternal and neonatal target attainment at delivery.MethodsData 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.ResultsAt 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.ConclusionsPopPK simulations showed that standard pre-delivery maternal cefazolin dosing provided adequate target attainment up to the time of delivery.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynecology and Reproductive Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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