Bioequivalence of Reference and Biosimilar Preparations of Premixed Biphasic Insulin Aspart: A Comparative Clamp Study.

Biphasic insulin aspart 30 is a premixed formulation containing a soluble fraction of insulin aspart (30%) and a protamine-crystallized fraction (70%) that was developed to combine the rapid-acting and prolonged advantages of commercially available insulins. The aim of this bioequivalence study was to compare the pharmacokinetics (PKs) of GP-bi-asp and Novo-bi-asp, and evaluate the pharmacodynamic (PD) properties as well as the safety of these drugs in the hyperinsulinemic euglycemic clamp (HEC) procedure. This was a phase 1, randomized, double-blind, 2-sequence, 2-period crossover study. Thirty-four male volunteers who met the inclusion criteria underwent the HEC procedure following a single subcutaneous injection of 0.4 IU/kg of either GP-bi-asp or Novo-bi-asp in the abdomen. After the treatment, the subjects' plasma glucose levels were monitored for 24 hours and the glucose infusion rate (GIR) was adjusted to maintain the target blood glucose level. The PD parameters were calculated using GIR values. Insulin aspart concentrations were measured in blood plasma using validated ELISA assays to evaluate the PK parameters of the investigated drugs. The 90% confidence intervals for the geometric mean ratios of PK (Cins and AUCins-T ) parameters of Gp-bi-asp and Novo-bi-asp were close to 100% and within the 80%-125% limits for establishing bioequivalence. The safety profiles of both drugs were also comparable.

Processes in auroral oval and outer electron radiation belt.

We have analyzed the role of auroral processes in the formation of the outer radiation belt, considering that the main part of the auroral oval maps to the outer part of the ring current, instead of the plasma sheet as is commonly postulated. In this approach, the outer ring current is the region where transverse magnetospheric currents close inside the magnetosphere. Specifically, we analyzed the role of magnetospheric substorms in the appearance of relativistic electrons in the outer radiation belt. We present experimental evidence that the presence of substorms during a geomagnetic storm recovery phase is, in fact, very important for the appearance of a new radiation belt during this phase. We discuss the possible role of adiabatic acceleration of relativistic electrons during storm recovery phase and show that this mechanism may accelerate the relativistic electrons by more than one order of magnitude.