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蛇毒的药代动力学。

Pharmacokinetics of Snake Venom.

机构信息

Clinical Toxicology Research Group, University of Newcastle, Newcastle 2298, Australia.

School of Pharmacy, University of Otago, Dunedin 9016, New Zealand.

出版信息

Toxins (Basel). 2018 Feb 7;10(2):73. doi: 10.3390/toxins10020073.

Abstract

Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974-present) and Medline (1946-present). For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, the disposition of snake venom was described by a two-compartment model consisting of a rapid distribution phase and a slow elimination phase, with half-lives of 5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms or toxins. When the venoms or toxins were administered intramuscularly or subcutaneously, an initial absorption phase and slow elimination phase were observed. The bioavailability of venoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following subcutaneous administration. The volume of distribution and the clearance varied between snake species. For humans, 24 out of 666 initially identified publications contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The data were extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an elimination half-life of 9.71 ± 1.29 h. It is intended that the quantitative information provided in this review will provide a useful basis for future studies that address the pharmacokinetics of snakebite in humans.

摘要

了解蛇毒药代动力学对于制定风险评估策略以及确定在蛇咬伤患者中结合所有毒液所需的抗蛇毒血清的最佳剂量和时间至关重要。本综述旨在探讨动物和人类蛇毒药代动力学的现有知识。使用 EMBASE(1974 年至今)和 Medline(1946 年至今)进行文献检索。对于动物,最初确定的 520 项研究中有 12 项符合纳入标准。一般来说,蛇毒的处置通过一个两室模型来描述,该模型由一个快速分布相和一个缓慢消除相组成,静脉内快速注射毒液或毒素后,半衰期分别为 5 至 48 分钟和 0.8 至 28 小时。当毒液或毒素肌肉内或皮下给药时,观察到初始吸收相和缓慢消除相。肌肉内给药后,毒液或毒素的生物利用度范围为 4%至 81.5%,皮下给药后为 60%。蛇种之间的分布容积和清除率有所不同。对于人类,最初确定的 666 项出版物中有 24 项包含足够的信息和抗蛇毒血清治疗前的定时毒液浓度,可用于提取数据。使用 NONMEM 提取和建模数据。单室模型提供了最佳拟合,消除半衰期为 9.71±1.29 小时。本综述提供的定量信息旨在为未来解决人类蛇咬伤药代动力学的研究提供有用的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d5b/5848174/b87987960e60/toxins-10-00073-g001.jpg

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