Bioavailability of repaglinide, a novel antidiabetic agent, administered orally in tablet or solution form or intravenously in healthy male volunteers

Objective: Repaglinide is a novel prandial glucose regulator (PGR) for the treatment of type 2 diabetes. In order to investigate subject variability f ollowing oral administration of repaglinide, and to determine the relative and absolute bioavailabilities of repaglinide following oral or intravenous administration, two single-centre, open-label, randomized, crossover clini cal studies were conducted. Subjects and methods: Study 1 was conducted in 24 healthy male subjects (aged 18 to 49 years), who received repaglinide 2 mg, as either tablet or oral solution, twice each on 4 separate occasions a t least 7 days apart. Study 2 was conducted in 12 healthy male subjects (ag ed 18 to 45 years), who received repaglinide 2 mg, either as a tablet or as an intravenous infusion over 15 minutes, once each on 2 separate occasions , with a washout period of 7 - 10 days. Results: In study 1 there was no si gnificant difference between administration of repaglinide 2 mg, in either tablet or oral solution form with regard to intrasubject variation in AUC a nd C-max. However, the intrasubject variation in t(max) and mean residence time (MRT) was significantly (p = 0.001) larger for the tablets than for th e oral solution. Intersubject variation (CV) in AUC ranged from 44.7% to 62 .1% after oral administration. The relative bioavailability of repaglinide (AUC(tablet)/AUC(oral) solution) was 110% (95% CI, 103% 117%). In study 2 t he absolute bioavailability of repaglinide administered as a tablet was 62. 5% (95 % CI, 49.2% - 79.5%) relative to an intravenous infusion of the same dose. Conclusion: There was no evidence from either study that the tablet formulation led to greater variation in serum profiles of repaglinide. It w as concluded that repaglinide is rapidly absorbed and eliminated in healthy subjects when administered orally or intravenously under fasting condition s, and that the total availability of repaglinide is similar in the tablet and oral solution formulations, though that the rate of absorption is slowe r for the tablet formulation.