Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
J Antimicrob Chemother. 2021 Nov 12;76(12):3229-3236. doi: 10.1093/jac/dkab329.
Intra-partum cefazolin is used to prevent group B Streptococcus (GBS) vertical transmission in mothers allergic to penicillin without a history of anaphylaxis.
To investigate the maternal cefazolin dose-exposure relationship and subsequent maternal and neonatal target attainment at delivery.
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.
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.
PopPK simulations showed that standard pre-delivery maternal cefazolin dosing provided adequate target attainment up to the time of delivery.
对于青霉素过敏且无过敏史的母亲，在产程中使用头孢唑林可预防 B 型链球菌（GBS）垂直传播。
研究产妇头孢唑林剂量-暴露关系及分娩时的母体和新生儿目标达成情况。
本研究数据来源于 24 名健康、GBS 定植的孕妇（年龄 20-41 岁），均行阴道分娩（胎龄≥37 周）。产程中，所有产妇均接受 2g 头孢唑林静脉滴注。若分娩延迟（>8 小时），8 小时后再次给予 1g。在每次给药间隔内（直至分娩），除了检测母体外周血浓度（最高达 10 次）外，还在分娩时检测静脉和动脉脐血浓度。以 60%的给药间隔（游离头孢唑林，最差临床折点）达到 1mg/L 作为母胎/新生儿血浆的目标达成。采用 NONMEM 7.4 建立群体药代动力学（popPK）模型。临床试验注册号：NCT01295606。
在分娩时，24 例产妇中有 23 例（95.8%）和 11 例（91.7%）的母体血液和动脉脐血中未结合的头孢唑林浓度>1mg/L。头孢唑林在孕妇中的 popPK 采用具有一级消除的两室模型描述。两个额外的隔室描述了静脉和动脉脐血浓度数据。在研究队列中，分娩发生在第一次或第二次剂量后不超过 6.5 小时，头孢唑林的目标达成是充分的。popPK 模拟显示，首次给药后 12 小时内母体和脐带的暴露是充分的。
popPK 模拟显示，标准的产前母亲头孢唑林给药方案在分娩时达到了充分的目标达成。
