Elkomy M H, Sultan P, Carvalho B, Peltz G, Wu M, Clavijo C, Galinkin J L, Drover D R
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California, USA; Department of Pharmaceutics and Industrial Pharmacy, Beni Suef University, Beni Suef, Egypt.
Clin Pharmacol Ther. 2015 Feb;97(2):167-76. doi: 10.1002/cpt.5. Epub 2014 Dec 4.
Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). The pharmacokinetics of ondansetron have not been characterized in pregnant women or in newborns. A nonlinear mixed-effects modeling approach was used to analyze plasma samples obtained from 20 nonpregnant and 40 pregnant women following a single administration of 4 or 8 mg ondansetron, from umbilical cord blood at delivery, and from neonates after birth. The analysis indicates that: ondansetron disposition is not affected by pregnancy (P > 0.05), but influenced by dose (P < 0.05), and is characterized by rapid transplacental transfer and longer elimination half-life in neonates compared to their mother. A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates.
昂丹司琼是剖宫产手术女性预防恶心的首选药物，也可用于预防新生儿戒断综合征（NAS）。昂丹司琼的药代动力学在孕妇或新生儿中尚未得到表征。采用非线性混合效应建模方法分析了20名非孕妇和40名孕妇单次服用4或8mg昂丹司琼后、分娩时脐血以及新生儿出生后的血浆样本。分析表明：昂丹司琼的处置不受妊娠影响（P>0.05），但受剂量影响（P<0.05），其特点是经胎盘快速转运，与母亲相比，新生儿的消除半衰期更长。基于该模型设计了预防NAS的给药方案。该方案包括在脐带夹紧前不久给母亲静脉注射4mg，或给新生儿口服0.07mg/kg（或等效于静脉注射0.04mg/kg）。
