| dc.description.abstract | The WHO mandates therapeutic interchangeability of multi-source oral medicines with the
respective innovator be proven either by bioequivalence (BE) or biowaiver. This study aimed to
evaluate the bioequivalence of two generic Metformin hydrochloride (MET) USP XR 500 mg oral
tablets (CIC Lifesciences Ltd., Sri Lanka) with the innovator Glucophage XR 500 mg (Merck Sante
S A S, France) in a randomized, two-treatment, two-period, two-sequence, open-label, singledose,
crossover trial under fasting conditions with one-week washout period. Eighteen healthy
subjects were recruited, and seventeen blood samples (4 mL each) were withdrawn from each
subject at different time points (0,1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24 h) after
administration of single dose of 1000 mg (500 mg x 2). Reverse-Phase High-Performance Liquid
Chromatography (RP-HPLC) UV spectrophotometric validated method with a mobile phase
consisted of Acetonitrile: water (25:75) with 20 mM of KH2PO4. Detection of metformin and
internal standard Ranitidine were done at 230 nm. Pharmacokinetic parameters Cmax, Tmax, area
under the plasma concentration-time curve zero-infinity (AUC0-∞), AUC0-t, were evaluated
statistically using PKMP version 1.03.28. The 90% confidence intervals for (test/reference) of
Cmax, Tmax AUC0-∞, AUC(0-t) were 96.88%-100.64%, 101.3%-108.871%, 103.39%-109.75% and
103.39%-109.75% respectively that fall within the recommended confidence interval (i.e.,
between 80-120%). The extent of absorption (AUC0 – ∞ and AUC0 – t) and the rate of absorption
(Cmax and Tmax) were not significantly different. Therefore, MET USP XR 500 mg oral tablet generic
CIC can be therapeutically interchangeable with innovator drug in clinical practice. | en_US |
