125I used for labelling of proteins in an absorption model changes the absorption rate of insulin aspart.
The aim of this study is to validate the ability of the disappearance model to predict absorption rates of insulin aspart in pigs. The disappearance model is used as a screening tool to estimate absorption rates after subcutaneous injections in humans or pigs especially of insulin and insulin analogues. The disappearance model measures remaining radioactivity at the injection site and therefore radioactive labelling of the insulin analogue is necessary. The labelling is done with 125I. One of the assumptions for the disappearance model to be reliable is that absorption rates of the labelled and non-labelled molecules are comparable. In this study, we compared disappearance data with absorption calculated from plasma samples of insulin aspart. The calculated absorption is based on non-labelled insulin aspart. The absorption rate from the disappearance data was statistical significant (p = 0.0028) different from the absorption rate based on plasma samples. A control study was carried out where 125I labelled insulin aspart was compared to 127I (the natural non-radioactive isotope) insulin aspart. In this study, absorption rate from the disappearance data and absorption rate based on plasma samples were similar (p = 0.63).


CONCLUSIONS
Iodination of insulin aspart changes the subcutaneous absorption rate.
Sohoel
Anders
A
Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark. anso@dfuni.dk
Plum
Anne
A
Frokjaer
Sven
S
Thygesen
Peter
P
D000042:Absorption; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D061267:Insulin Aspart; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D008954:Models, Biological; D012588:Scintillation Counting; D013552:Swine
D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D061267:Insulin Aspart