Abstract
Insulin is a frequently prescribed drug in hospitals and is usually administered by syringe pumps with an extension line which can be made of various materials. Two insulin solutions were studied: an insulin analogue, Novorapid® which contains insulin aspart and two phenolic preservatives (e.g. phenol and metacresol) and Umuline rapide® with human insulin and metacresol as preservative. Some studies have indicated interactions between insulin, polyvinyl chloride (PVC) and polyethylene (PE). The aim of this work was to study such interactions between Novorapid® or Umuline rapide® and infusion extension line materials (PVC, PE and coextruded (PE/PVC)). Insulin solution at 1 IU/mL was infused at 2 mL/h over 24 hours with 16 different extension lines (8 in PVC, 3 in PE and 5 in PE/PVC). Ultra-Fast Liquid Chromatography with diode array detection (UFLC-DAD) was performed to quantify insulin (human and aspart) and preservatives (metacresol and phenol). Limited human insulin sorption was observed thirty minutes after the onset of infusion: 24.3 ± 12.9%, 3.1 ± 1.6% and 18.6 ± 10.0% for PVC, PE and PE/PVC respectively. With insulin aspart, sorption of about 5% was observed at the onset of infusion for all materials. However, there were interactions between phenol and especially metacresol with PVC, but no interactions with PE and PE/PVC. This study shows that insulin interacts with PVC, PE and PE/PVC at the onset of infusion. It also demonstrates that insulin preservatives interact with PVC, which may result in problems of insulin conservation and conformation. Some more studies are required to understand the clinical impact of the latter during infusion.
Highlights
Several studies have already been made describing interactions between insulin and infusion lines
Hewson et al [2] conducted a study on Actrapid1 adsorption on extension tubing in di (2-ethylhexyl) phthalate (DEHP)—plasticized polyvinyl chloride (PVC) in a neonatal unit
They measured insulin by radioimmunoassay, and concluded that insulin was adsorbed on PVC and that this was increased by low concentrations and flow rates
Summary
Several studies have already been made describing interactions between insulin and infusion lines. Hewson et al [2] conducted a study on Actrapid adsorption on extension tubing in di (2-ethylhexyl) phthalate (DEHP)—plasticized PVC in a neonatal unit They measured insulin by radioimmunoassay, and concluded that insulin was adsorbed on PVC and that this was increased by low concentrations and flow rates. Adsorption of insulin lispro and regular human insulin [6] has been studied with intravenous infusion sets in PVC and syringes in polypropylene These authors studied the effects of the absence or presence of an in-line filter on the release profile of insulin lispro by high pressure liquid chromatography. Hewson et al [2] used albumin to reduce insulin adsorption on the catheter All these strategies are rarely used in hospitals, it is important for clinicians to take into account interactions between drugs and infusion line materials. The main objective of this work was to study the influence of intravenous extension set material on insulin aspart delivery (maintaining its complete pharmaceutical formula); the secondary objectives were to compare the drug delivery of insulin aspart versus human insulin and evaluate the interactions of preservatives with various materials
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