Pharmacokinetics and dose proportionality of extended‐release metformin following administration of 1000, 1500, 2000 and 2500 mg in healthy volunteers

The pharmacokinetics and dose‐exposure relationship of an extended‐release formulation of metformin (ER‐metformin) was investigated in a randomized, single‐dose, four‐period crossover study in 24 healthy male volunteers. During each study period, subjects received a randomly assigned dose containing 1000, 1500, 2000 or 2500 mg metformin. Blood samples were drawn 0–72 h after dosing for pharmacokinetic and dose‐proportionality assessment. Although several pairwise comparisons between dose groups were significant ( p <0.05) with respect to dose‐normalized C max , AUC 0–72 h , and AUC ∞ , the magnitude of the difference across the dose range was <20% for AUC 0–72 h and AUC ∞ , and was ⩽30% for C max . The results indicate a consistent and predictable increase in metformin exposure with an extended‐release formulation of metformin over 1000 to 2500 mg. Copyright © 2004 John Wiley & Sons, Ltd.