基于生理学的药代动力学模型指导新生儿舌下含服丁丙诺啡后的唾液治疗监测

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Therapeutic Drug Monitoring Pub Date : 2024-08-01 Epub Date: 2024-02-16 DOI:10.1097/FTD.0000000000001172
Mo'tasem M Alsmadi
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引用次数: 0

摘要

背景:孕期阿片类药物使用障碍(OUD)与高死亡率和新生儿阿片类药物戒断综合征(NOWS)有关。丁丙诺啡是一种阿片类药物,可用于治疗 OUD 和 NOWS。丁丙诺啡的活性代谢物(诺丁诺啡)可穿过胎盘,并在脑细胞外液(bECF)浓度较高时导致新生儿呼吸抑制(EC50 = 35 ng/mL)。使用唾液进行新生儿治疗药物监测可减少频繁抽血带来的痛苦和感染:方法:我们构建了一个基于成人生理的丁丙诺啡和去甲丁丙诺啡静脉注射和舌下含服药代动力学模型,对该模型进行了审核,并将其应用于新生儿和妊娠人群。妊娠模型预测丁丙诺啡和诺丁诺啡的剂量会通过胎盘转移到新生儿体内。新生儿生理药代动力学模型用于估算服用这些剂量后新生儿血浆、bECF 和唾液中丁丙诺啡和诺丁诺啡的水平:结果:母体舌下含服丁丙诺啡(4 毫克/天)后,新生儿血浆中丁丙诺啡和诺丁诺啡的估计浓度分别在 8 小时和 24 小时内超过毒性阈值。不过,诺丁诺啡的 bECF 水平低于呼吸抑制阈值。此外,新生儿唾液中丁丙诺啡镇痛、诺丁诺啡镇痛和诺丁诺啡通气不足的阈值水平分别为 22、2 和 162 纳克/毫升:结论:使用新生儿唾液进行丁丙诺啡治疗药物监测可促进新生儿在母亲使用舌下丁丙诺啡治疗 OUD 期间的安全性。尽管如此,对新生儿使用成人呼吸抑制 EC50 值是否合适仍有待确认。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Salivary Therapeutic Monitoring of Buprenorphine in Neonates After Maternal Sublingual Dosing Guided by Physiologically Based Pharmacokinetic Modeling.

Background: Opioid use disorder (OUD) during pregnancy is associated with high mortality rates and neonatal opioid withdrawal syndrome (NOWS). Buprenorphine, an opioid, is used to treat OUD and NOWS. Buprenorphine active metabolite (norbuprenorphine) can cross the placenta and cause neonatal respiratory depression (EC 50 = 35 ng/mL) at high brain extracellular fluid (bECF) levels. Neonatal therapeutic drug monitoring using saliva decreases the likelihood of distress and infections associated with frequent blood sampling.

Methods: An adult physiologically based pharmacokinetic model for buprenorphine and norbuprenorphine after intravenous and sublingual administration was constructed, vetted, and scaled to newborn and pregnant populations. The pregnancy model predicted that buprenorphine and norbuprenorphine doses would be transplacentally transferred to the newborns. The newborn physiologically based pharmacokinetic model was used to estimate the buprenorphine and norbuprenorphine levels in newborn plasma, bECF, and saliva after these doses.

Results: After maternal sublingual administration of buprenorphine (4 mg/d), the estimated plasma concentrations of buprenorphine and norbuprenorphine in newborns exceeded the toxicity thresholds for 8 and 24 hours, respectively. However, the norbuprenorphine bECF levels were lower than the respiratory depression threshold. Furthermore, the salivary buprenorphine threshold levels in newborns for buprenorphine analgesia, norbuprenorphine analgesia, and norbuprenorphine hypoventilation were observed to be 22, 2, and 162 ng/mL.

Conclusions: Using neonatal saliva for buprenorphine therapeutic drug monitoring can facilitate newborn safety during the maternal treatment of OUD using sublingual buprenorphine. Nevertheless, the suitability of using adult values of respiratory depression EC 50 for newborns must be confirmed.

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来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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