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Population pharmaco...
Population pharmacokinetics of cefazolin in maternal and umbilical cord plasma, and simulated exposure in term neonates
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- Elkayal, Omar (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.
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- Allegaert, Karel (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;Katholieke Univ Leuven, Dept Dev & Regenerat, Leuven, Belgium.;Erasmus MC, Dept Clin Pharm, Rotterdam, Netherlands.
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- Spriet, Isabel (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
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- Smits, Anne (author)
- Katholieke Univ Leuven, Dept Dev & Regenerat, Leuven, Belgium.;Univ Hosp Leuven, Neonatal Intens Care Unit, Leuven, Belgium.
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- Seghaye, Marie-Christine (author)
- Ctr Hosp Univ Liege, Dept Paediat, Liege, Belgium.
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- Charlier, Corinne (author)
- Ctr Hosp Univ Liege, Dept Toxicol, Liege, Belgium.
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- Dreesen, Erwin (author)
- 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)
- 2021-09-09
- 2021
- English.
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In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 76:12, s. 3229-3236
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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