Remaining Level of Octreotide Administered by Mixed Injection into ELNEOPA No 1

Abstract

Octreotide is often administered to patients by addition to total parenteral nutrition (TPN) as well as by subcutaneous injection. However, the concentration has not been determined to remain greater than 90％ through the completion of its administration. This study investigated the stability of octreotide during administration in ELNEOPA No 1 TPN solution, a four-chambered duplex delivery system. The level of octreotide in the upper-chamber of the ELNEOPA No 1 duplex delivery system, pH 4.0, remained stable, whereas that in the lower chamber, pH 7.0, decreased to less than 90％ of the initial concentration immediately after mixing. The final concentration of octreotide in pH 7.5 buffer solution was significantly lower than that in pH 5.1 buffer solution. The influence of pH was reversible. However, a fraction of octreotide suffered decomposition in pH 7.5 buffer solution. Hence, it might be suitable to inject octreotide into the upper chamber that has the lowest pH among the 4 chambers of the duplex drug delivery system used by ELNEOPA No 1. Reducing agents such as sodium hydrogen sulfite caused the concentration of octreotide to decrease. Although the mixed solution of the 4 chambers contains sodium hydrogen sulfite, the concentration of octreotide remained greater than 90％ for about 3 days. The decrease in concentration caused by sodium hydrogen sulfite seemed to be protected by the co-presence of glucose or cysteine. The results of our octreotide concentration studies suggest the possibility that the therapeutic effects of octreotide administered via TPN would be equivalent to the effects following subcutaneous administration.