Dor Eyal, David Tseela, Dekel Jaoui Hani, Schwartz Arieh, Baruchi Tzadok, Torgeman Amram, Ben David Alon, Rosen Osnat, Tal Arnon, Rosner Amir, Zichel Ran, Diamant Eran
Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel.
Veterinary Center for Pre-clinical Research, Israel Institute for Biological Research, Ness Ziona, Israel.
Front Pharmacol. 2021 Apr 8;12:637792. doi: 10.3389/fphar.2021.637792. eCollection 2021.
Medical treatment may require the continuous intravenous (IV) infusion of drugs to sustain the therapeutic blood concentration and to minimize dosing errors. Animal disease models that ultimately mimic the intended use of new potential drugs via a continuous IV infusion in unrestrained, free roaming animals are required. While peripherally inserted central catheters (PICCs) and other central line techniques for prolonged IV infusion of drugs are prevalent in the clinic, continuous IV infusion methods in an animal model are challenging and limited. In most cases, continuous IV infusion methods require surgical knowledge as well as expensive and complicated equipment. In the current work, we established a novel rabbit model for prolonged continuous IV infusion by inserting a PICC line from the marginal ear vein to the superior vena cava and connecting it to an externally carried ambulatory infusion pump. Either saline or a clinically relevant formulation could be steadily and continuously infused at 3-6 ml/h for 11 consecutive days into freely moving rabbits while maintaining normal body temperature, weight, and respiration physiology, as determined by daily spirometry. This new model is simple to execute and can advance the ability to administer and test new drug candidates.
药物治疗可能需要持续静脉输注药物,以维持治疗所需的血药浓度并尽量减少给药误差。需要建立动物疾病模型,通过在不受约束、自由活动的动物身上持续静脉输注,最终模拟新潜在药物的预期用途。虽然外周静脉穿刺中心静脉导管(PICC)和其他用于长时间静脉输注药物的中心静脉置管技术在临床上很普遍,但在动物模型中进行持续静脉输注的方法具有挑战性且受到限制。在大多数情况下,持续静脉输注方法需要外科知识以及昂贵且复杂的设备。在当前的研究中,我们建立了一种新型兔模型,通过从耳缘静脉插入PICC导管至头臂静脉,并将其连接到外部携带的便携式输液泵,实现长时间持续静脉输注。通过每日肺活量测定法确定,无论是生理盐水还是临床相关制剂,都可以以3 - 6毫升/小时的速度稳定、持续地连续输注11天,同时保持自由活动兔子的正常体温、体重和呼吸生理状态。这种新模型操作简单,能够提升给药和测试新候选药物的能力。