利用PBPK模型分析肌内给药孕妇宫内暴露后新生儿唾液、血浆和脑外胞液中哌替啶的药代动力学

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Mo'tasem M Alsmadi, Nasir Idkaidek
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引用次数: 2

摘要

背景与目的:哌替啶(哌替啶)可降低产痛相关的产妇过度通气和高皮质醇引起的新生儿并发症。然而,产前经胎盘获得性哌替啶可引起新生儿的副作用。新生儿脑细胞外液(bECF)中高哌啶浓度可引起血清素危机。新生儿血液中的治疗性药物监测(TDM)使新生儿感到痛苦,增加了感染的发生率,这可以通过唾液TDM来克服。基于生理的药代动力学(PBPK)模型可以预测宫内哌替啶暴露后新生儿血浆、唾液和bECF中的药物浓度。方法:建立健康成人静脉和肌注哌替啶后PBPK模型,对模型进行验证,并将模型扩展到新生儿和孕妇。采用妊娠PBPK模型预测新生儿出生时经胎盘给药剂量,将经胎盘给药剂量作为新生儿PBPK模型的输入,预测新生儿血浆、唾液、bECF哌替啶浓度,并建立相关方程。结果:哌替啶可归入唾液排泄分类系统ⅱ类药物。建立的PBPK模型预测,母亲肌肉注射100 mg和150 mg哌啶后,新生儿血浆和bECF浓度低于毒性阈值。此外,据估计,新生儿唾液浓度分别为4.7µM、11.4µM和57.7µM可作为哌替啶镇痛作用、副作用和血清素危机风险的唾液阈值浓度。结论:唾液可用于新生儿在分娩后几天服用哌啶的母亲的哌啶TDM。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Analysis of Pethidine Pharmacokinetics in Newborn Saliva, Plasma, and Brain Extracellular Fluid After Prenatal Intrauterine Exposure from Pregnant Mothers Receiving Intramuscular Dose Using PBPK Modeling.

The Analysis of Pethidine Pharmacokinetics in Newborn Saliva, Plasma, and Brain Extracellular Fluid After Prenatal Intrauterine Exposure from Pregnant Mothers Receiving Intramuscular Dose Using PBPK Modeling.

Background and objective: Pethidine (meperidine) can decrease labor pain-associated mother's hyperventilation and high cortisol-induced newborn complications. However, prenatal transplacentally acquired pethidine can cause side effects in newborns. High pethidine concentrations in the newborn brain extracellular fluid (bECF) can cause a serotonin crisis. Therapeutic drug monitoring (TDM) in newborns' blood distresses them and increases infection incidence, which can be overcome by using salivary TDM. Physiologically based pharmacokinetic (PBPK) modeling can predict drug concentrations in newborn plasma, saliva, and bECF after intrauterine pethidine exposure.

Methods: A healthy adult PBPK model was constructed, verified, and scaled to newborn and pregnant populations after intravenous and intramuscular pethidine administration. The pregnancy PBPK model was used to predict the newborn dose received transplacentally at birth, which was used as input to the newborn PBPK model to predict newborn plasma, saliva, and bECF pethidine concentrations and set correlation equations between them.

Results: Pethidine can be classified as a Salivary Excretion Classification System class II drug. The developed PBPK model predicted that, after maternal pethidine intramuscular doses of 100 mg and 150 mg, the newborn plasma and bECF concentrations were below the toxicity thresholds. Moreover, it was estimated that newborn saliva concentrations of 4.7 µM, 11.4 µM, and 57.7 µM can be used as salivary threshold concentrations for pethidine analgesic effects, side effects, and the risk for serotonin crisis, respectively, in newborns.

Conclusion: It was shown that saliva can be used for pethidine TDM in newborns during the first few days after delivery to mothers receiving pethidine.

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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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