Aims/hypothesis: Pharmacokinetics of s.c. administered insulin preparations have been widely studied, mostly using descriptive measures such as AUC, time to peak, or the peak plasma concentration. Several compartmental modelling studies of single-bolus s.c. insulin pharmacokinetics have also appeared, with contrasting results regarding the feasibility of insulin pharmacokinetics modelling and the appropriate level of detail for such models. In this paper, we used compartmental models to study the pharmacokinetics of biphasic insulin aspart administered by multiple s.c. injections. The main objective was to assess the magnitude of the inter-and intra-subject variation in the kinetics.
Materials and methods: Analyses were performed on 24-h serum insulin concentrations measured in 20 type 1 diabetes subjects given three daily s.c. injections of biphasic insulin aspart.
Results: Preliminary analysis of the AUC:dose ratio showed that the apparent kinetics are not constant throughout the three daily injections of the compound. A simple and robust compartmental model was shown to be appropriate for interpreting the observations, provided that one of its parameters (the first-order rate constant for transfer from the s.c. depot to plasma) is allowed to vary between injections.
Conclusions/interpretation: Population estimates of the chosen model show that intra-subject variations between injections is of the same order of magnitude as inter-subject variation, partially explaining the difficulties encountered when individually tailoring intensified insulin therapy. We conclude that the explicit consideration of a rather simple kinetic model will allow better experimental designs in the future study of s.c. insulin preparations.