Metformin IR versus XR Pharmacokinetics in Humans

Pharmacokinetics of metformin extended release (XR) formulation were studied under fasting and fed conditions and compared to those of immediate release (IR) under fasting conditions in humans. 78 healthy human volunteers participated in 3 independent studies (26 subjects per study) were given either 1000 mg oral dose metformin IR or 750 mg metformin XR. Plasma samples were obtained up to 24 hours after dosing. Pharmacokinetic parameters in plasma were calculated by non compartmental analysis using Kinetica program. Results have shown increased XR bioavailability and delayed time to reach the maximum concentration (Cmax ) in the fed state as compared to fasted state, with no significant difference in Cmax and half life values. On the other hand, the IR formulation showed significant differences in all parameters as compared to XR formulation, yet the half life was similar. In conclusion, XR formulation was shown similar to IR formulation with less possible side effects.