Fiche publication
Date publication
octobre 2010
Résumé
Since 1996, genetic engineering has allowed modifications of insulin yielding to multiple modified insulins with different pharmacokinetic and/or pharmacodynamic properties. Molecules with maintained pharmacodynamic and modified pharmacokinetic profiles have been selected. Currently available rapid-acting analogues (lispro, aspart and glulisine) achieve plasma peak concentrations about twice as high and within approximately half the time compared with regular human insulin thus closely mimicking the physiological insulin response to a meal. Long-acting analogues (glargine and detemir) ensure the steady supplement of basal insulin plasma levels, with a plateau type of profile. Main analytical pitfalls of commercially human insulin immunoassays include crossreactivity with analogues and their metabolites. These crossreactivities are of great concern for interpreting insulin levels in patients treated with analogues. The development of more specific analytical methods to quantify separately the concentrations of endogenous insulin, rapid-acting and long-acting analogues and metabolites would be of utmost importance: (1) to further understand long-acting analogue variability in terms of efficiency; (2) to perform analogue kinetic studies; (3) to measure analogues in routine toxicology (forensic medicine) and (4) to assess intact glargine or glargine metabolite in vivo toxicity: recent debates about glargine safety have highlighted the lack of data about metabolite status (proportion of metabolized glargine and bioactivity of its metabolite). This goal could be achieved by specific immunoassay development or/and mass spectrometry analysis. (C) 2010 Published by Elsevier Masson SAS.
Référence
Med Nucl-imag Fonct Metab. 2010 Oct;34(10):571-82.
