3PC-003 Terlipressin pH stability for continuous infusion

Background and importance Terlipressin is a synthetic vasoconstrictor peptide similar to desmopressin, used to treat bleeding oesophageal varices and hepatorenal syndrome. Recent publications have shown greater efficacy via continuous infusion (CI) compared with intermittent bolus injection. This could be explained by its pharmacodynamic effect ( Aim and objectives The objective of the study was to determine the pH variation after dilution of terlipressin in different diluents commonly used in clinical practice for administration as a CI. Material and methods The diluents used were 0.9% NaCl (NS), 5% dextrose (D5W) and 3.3% dextrose–0.3% saline (DS). The initial pH measurement was performed with the commercial ampoule (8.5 mL) after reaching room temperature, as well as with the diluents separately. Subsequently it was diluted to 10, 20, 50, 100, 200, 250 and 500 mL. Triplicate pH measurements were made. The whole process was carried out at 23°C with a precision pH meter WTW inoLab pH level 1. Results Initial pH values were: 3.94±0.04 terlipressin, 5.62±0.10 NS, 6.14±0.04 D5W and 4.64±0.04 DS. In NS, up to 10 and 20 mL, a slight decrease in pH was observed up to 3.92±0.03. Subsequently, the value increased exponentially, reaching a pH of 4.11±0.06 in 500 mL of NS. This initial behaviour was only observed with NS, while with D5W and DS the pH increase was exponential with the increase in volume, until reaching pH values of 4.15±0.01 and 4.13±0.02, respectively, at 500 mL. In all three cases, a tendency to reach pH values >4 was observed, values in which the stability of the molecule would be compromised. Conclusion and relevance The results show that pH values are within the terlipressin stability range. This makes it possible to dilute terlipressin with NS, D5W and DS in volumes between 50 and 500 mL (not higher), allowing administration in 24 hours by CI, reducing the dose and number of administrations. References and/or acknowledgements No conflict of interest.