Compatibility of Insulin over 24 Hours in Standard and Bicarbonate-Based Peritoneal Dialysis Solutions Contained in Bags Made of Different Materials

Abstract

Background The purpose of this study was to evaluate potency changes in insulin in different solutions and bag materials used for peritoneal dialysis (PD). One of the PD solutions (Physioneal) tested is available in two different solution containers, PVC and Clear-Flex. Four insulin concentrations (4 IU/L, 10 IU/L, 20 IU/L, and 40 IU/L) were evaluated. This range of concentrations was defined in accordance with standard medical practice. All PD solutions made by Baxter, Castlebar, Ireland. Methods Insulin determination was performed by immunoassay (ELISA). Results In Dianeal, more than 90% of the initial dose of insulin remained available up to 24 hours for all concentrations tested. In Physioneal, for the higher concentrations tested (10 IU/L, 20 IU/L, and 40 IU/L), more than 90% of the initial dose of insulin remained available up to 6 hours, and more than 80% up to 24 hours. For the lowest concentration of insulin tested in Physioneal (4 IU/L), more than 90% of the initial dose of insulin remained available up to 3 hours, and more than 70% up to 24 hours. Also for the lowest concentration of insulin, recovery correlated with the pH of the tested solutions. This effect became apparent over the storage time. Conclusions The data show that insulin adsorption is less than 10% during the first 3 hours for every PD solution tested. Insulin recovery tends to be stable or to decrease slightly over time for the lower insulin concentrations tested. The results for insulin recovery show a correlation with insulin concentration and with pH for the lowest insulin dose tested. From a solution–container interaction perspective, Clear-Flex is an equivalent alternative to standard PVC material.

Intraperitoneal Administration of Drugs in Peritoneal Dialysis Patients: A Review of Compatibility and Guidance for Clinical Use

“…While no significant differences in adsorption of insulin are observed between PVC and polyolefin containers (30), adsorption to glass surfaces is much faster and more pronounced (29). Recently, Voges et al demonstrated that insulin agglomeration (31), which occurs with increasing pH, was concomitant with increased adsorption (30). Generally, if adsorption occurs, the adsorption behavior of any drug seems similar to that of insulin in terms of time, temperature, and concentration.…”

“…Table 2 lists stability data of drugs studied as single additives to PD solutions in PVC containers (30,35-38,45-50,52,54-71). For drugs for which stability differs with concentration and/or PD solution formulation, corresponding stabilities are given; otherwise, the reported stability is applicable to all combinations.…”

“…The percentage of insulin adsorbed to PVC material increases with time and temperature and decreases with increasing insulin concentrations (29). While no significant differences in adsorption of insulin are observed between PVC and polyolefin containers (30), adsorption to glass surfaces is much faster and more pronounced (29). Recently, Voges et al demonstrated that insulin agglomeration (31), which occurs with increasing pH, was concomitant with increased adsorption (30).…”

“…Among the data gathered, only in two papers were all aspects of drug compatibility investigated (30,44). In only 38% of the reports, in addition to drug stability, was diluent stability examined by both visual inspection and pH monitoring (30,38,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). Moreover, many studies lacked the use of blank PD solution as a reference.…”

Peritoneal Dialysis in Diabetics: There Is Room for More

“…The reduction in insulin requirement is most pronounced compared with subcutaneous administration when insulin is instilled into the empty abdominal cavity, but if insulin is instilled with dialysis solution, there are losses of activity due to adsorption to the plastic surface of delivery systems [ 25 ]. Besides, bioavailability of intraperitoneal insulin might differ according to the solution bag used [ 26 ]. Importantly, hepatic subcapsular steatosis may be a complication associated with intraperitoneal insulin [ 27 ].…”