PP082—Prescription of recommended drugs for acute myocardial infarction in Estonia in 2001 vs 2007 and in 2007 vs 2011

2013 e43 Patients (or Materials) and Methods: New insulin analogue AKR of a potential long-acting feature was evaluated in the Institute of Biotechnology and Antibiotics. Bioactivity of AKR was compared with that of USP human insulin standard in bioassays on cells and rabbits, while the pharmacodynamic activity on rats was referred to control group received 0.9% NaCl. The 3T3-L1 cells differentiated into adipocytes were used for the performance of insulin dependent glucose uptake experiment. Dose-response relationship of log insulin concentration and Deoxy-D-glucose uptake of AKR was determined. The biological activity on animals was assessed on 24 albino rabbits according to US Pharmacopeia. The glucose concentrations were measured with spectrophotometer in 2 time points (1.0 and 2.5 hours) after administration of 1 U and 2 U of insulin. Potency of AKR was calculated with 95% CI. Pharmacodynamic effect was based on glucose concentration measurement in rats with hyperglycemia induced by streptozotocin. The overall glycemic profile up to 36 hours was evaluated after subcutaneous single dosing at range 2.5 to 10.0 U/kg b.w. In the 28-day multiple dose study, AKR was administered twice a day at dose 5.0 U/kg b.w. Results: Percentage of maximum Deoxy-D-glucose uptake in 3T3L1 cells was similar for AKR and human insulin, except the highest concentration in which the hook effect was observed. The absolute potency of a new analogue determined in rabbits was 23.94 U/mg, and the potency ratio of AKR versus the insulin standard was 0.90. The relative potency was 38.35 U/mL with confidence limit of 32.99– 44.42 U/mL. The experiment on rats confirmed with a statistical significance (P < 0.05) hypoglycemic activity of AKR in comparison of control group both after single and multiple doses. Characteristics for AKR profile was rather fast beginning of action (0.5-1.0 hour) with the maximal effect at 6 hours postdose and quite prolonged return to initial values. The glucose levels were stable during 4-week administration. Conclusion: Bioactivity of the novel insulin analogue AKR, connected with glucose metabolism was confirmed in both in vitro and in vivo conditions. AKR is a candidate for a hypoglycemic drug product in diabetes care. Financial Source: Supported by European Regional Development Found, POIG.01.01.02-00-007/08. Disclosure of Interest: None declared.