Precipitation of insulin aspart and insulin glulisine products used for continuous subcutaneous insulin infusion.

BACKGROUND

The commercially available insulin products insulin aspart injection (IAsp) and insulin glulisine injection (IGlu), used for continuous subcutaneous insulin infusion (CSII), have been compared with respect to resistance towards isoelectric insulin precipitation. Additionally, a hybrid product consisting of the insulin aspart analogue in an IGlu product composition (the hybrid product was termed IAsp (Apidra)) has been examined.

METHODS

The degree of isoelectric insulin precipitation was examined by reverse-phase high performance liquid chromatography while reducing pH through addition of diluted HCl.

RESULTS

The pH at which isoelectric precipitation occurred differed between IAsp and IGlu as reflected by the pH level at which 50% of the insulin precipitated (IAsp, pH 5.86; IGlu, pH 6.64). The amount of H(+)-equivalents per microliter of product required to induce isoelectric precipitation differed between IAsp and IGlu as reflected by the amount of acid required to cause 50% insulin precipitation (5.27 and 4.14 nmol of H(+)-equivalents, respectively). Data from IAsp(Apidra) suggest that the observed difference between IAsp and IGlu can be attributed to a combination of the different insulin analogue molecules and different product compositions of IAsp and IGlu.

CONCLUSIONS

Resistance towards isoelectric precipitation is highest for IAsp and lowest for IGlu because of the lower pH and higher amount of acid required to induce isoelectric insulin precipitation of IAsp. Isoelectric precipitation will alter the pharmacokinetic properties of the insulin and could lead to occlusion of the infusion catheter during CSII. However, further studies are required to elucidate the potential clinical relevance of the observed differences in in vitro resistance towards isoelectric precipitation between IAsp and IGlu.