Abstract

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.

Highlights

  • Discovering new drug therapies through the infusion of compounds into the vascular system involves examining the potential effects of drugs in an animal disease model (Nolan and Klein, 2002; Yu, 2011)

  • The main objective of the current study was to establish a rabbit model for prolonged continuous IV infusion using a peripherally inserted central catheters (PICCs)-based technique combined with daily spirometry

  • Following PICC insertion, the catheter was aseptically connected to a carried minipump, and a continuous infusion of either saline or Sol/Benz was initiated at 3–6 ml/ h and maintained for 11 consecutive days

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Summary

Introduction

Discovering new drug therapies through the infusion of compounds into the vascular system involves examining the potential effects of drugs in an animal disease model (Nolan and Klein, 2002; Yu, 2011). To mimic human pharmacokinetics (PK), as well as pharmacodynamics (PD), continuous infusion of therapeutic compounds, such as antimicrobials and small molecule inhibitors that suffer from rapid clearance, should be utilized in animal models (Zhao et al, 2016). Various infusion systems for long-term vascular access have been used for several decades in preclinical studies with different animal models, from small rodents to horses (Lemmel and Good, 1971; Burrows, 1973; Burt et al, 1980; DaRif and Rush, 1983; Aguiar et al, 1988; Sellon et al, 2001; Laliberte et al, 2005; Turner et al, 2011), both catheterization techniques and delivery systems still pose major challenges.

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