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( infinity ), the magnitude of the difference across the dose range was <20% for AUC(0-72 h) and AUC( infinity ), and was < or = 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.
Cullen
Edward
E
Andrx Laboratories, Hackensack, NJ 07601, USA. eic@pspg.com
Liao
James
J
Lukacsko
Peter
P
Niecestro
Robert
R
Friedhoff
Lawrence
L
D000284:Administration, Oral; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D008687:Metformin