5) to rats. When insulin glargine alone was injected, the maximum level (Cmax ) of insulin glargine and the time (Tmax ) required to the reach Cmax after injection were 150 μU/mL and 1.00h, respectively. In the presence of SBE7-β-CyD (200mM), Cmax significantly decreased to 91.60 μU/mL although Tmax did not change remarkably, compared to that of insulin glargine alone. The area under the serum insulin glargine level-time curve (AUC) in the SBE7-β-CyD system (200mM) up to 12h (687.86 (μU/mL)·h) was significantly increased, compared to those of insulin glargine alone (582.99 Inhibitors,research,lifescience,medical (μU/mL)·h). In addition, SBE7-β-CyD (200mM) extended the mean residence time (MRT) of

the serum insulin glargine level significantly, Inhibitors,research,lifescience,medical comparing with that of insulin glargine alone. These results indicate that SBE7-β-CyD sustained the serum insulin glargine level. Figure 7 Effects of SBE7-β-CyD (200mM) on serum insulin glargine (a) and glucose (b) levels after subcutaneous administration of insulin glargine (2IU/kg) to rats. Each point represents the mean ± S.E.M. of 4–6 experiments. … Table 2 In vivo pharmacokinetics parameters of insulin glargine with or without SBE7-β-CyD (200mM). (1) Time required Inhibitors,research,lifescience,medical to reach the maximum serum insulin glargine level. (2) Maximum serum insulin glargine level. (3) Area under the serum … Figure 7(b) and Table 3 show the serum glucose level-time profiles and pharmacodynamics

parameters after subcutaneous administration of insulin glargine (2IU/kg) with or without SBE7-β-CyD (200mM) in the phosphate buffer (pH 9.5) to rats. When insulin glargine alone was administered, the time to nadir blood glucose concentration (Tnadir) was 1.6h after injection, and then Inhibitors,research,lifescience,medical the blood glucose levels recovered within 6h to basal level. On the Inhibitors,research,lifescience,medical other hand, insulin glargine administered with SBE7-β-CyD significantly Bortezomib supplier retained the blood-glucose lowering effect up to 6h after administration. Tnadir was significantly increased in the insulin glargine/SBE7-β-CyD system. Further, the insulin glargine/SBE7-β-CyD system showed the tendency to augment the area under

serum glucose level-time curve (AUCG). The retained blood-glucose lowering effects and enhancement of Tnadir by the addition of SBE7-β-CyD may be contributed to (1) the inhibitory effects of SBE7-β-CyD on the enzymatic degradation of insulin glargine (Figure 6) and (2) the enhancement of solubility and the dissolution nearly rate of insulin glargine by SBE7-β-CyD (Figures ​(Figures33–5). However, the enhancement of bioavailability and persistence of the blood-glucose lowering effect of insulin glargine after subcutaneous injection to rats by SBE7-β-CyD was not superior to that of SBE4-β-CyD. The reason for this may be due to the difference in adsorption of insulin glargine onto the subcutaneous tissue at injection site between the SBE7-β-CyD and SBE4-β-CyD systems [19].