| dc.description.abstract | The World Health Organization (WHO) requires bioequivalence studies to evaluate if
medication from various sources are therapeutically equivalent to the innovator product.
In this study, the bioequivalence of generic metformin hydrochloride XR 500 mg (Gamma
Interpharm Ltd) was compared to the innovator, glucophage XR 500 mg (Merck Sante S
A S, France). This study was a randomized, two- treatment, two-period, two-sequence,
open-label, single-dose, with crossover design, under fasting conditions, with a one-week
washout, in twenty (20) healthy Sri Lankans. Seventeen blood samples were collected
at time points (0, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7 , 8, 10, 12, 16, 24 h) post-oral dose of 500 mg x2. Metformin plasma levels were assessed with validated Reverse Phase High-Performance Liquid Chromatography UV spectrophotometry. The mobile
phase was acetonitrile and phosphate buffer 20 mM (KH2PO4) in a 50:50 (v/v) ratio.
Metformin and internal standard, ranitidine, were detected at 230 nm. Pharmacokinetic
parameters Cmax (maximum plasma concentration), Tmax (time to reach Cmax), the
area under the plasma concentration-time curve (AUC 0-infinity), and area under the
plasma concentration-time curve from 0 to last measurable concentration (AUC 0-t) were
analyzed statistically using PKMP (version 1.05, 2017, APL, USA). The 90% confidence
intervals for Cmax, Tmax, AUC0-infinitive, and AUC 0-t (test/reference) were 97.97% -
103.89%, 99.45% - 105.37%, 94.42 - 108.38%, and 97.16% - 108.65% respectively. These were
within the acceptable range (80-120%), indicating that the extent and rate of absorption
of the two formulations did not differ significantly. Therefore, they can be considered
therapeutically interchangeable (i.e. bioequivalent) in clinical practice. | |
