Pharmacokinetic and pharmacodynamic comparison between Glucophage? and a generic metformin in a rat model

doi:10.5246/jcps.2019.02.013

Abstract

Abstract:

In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage^®and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic formulation.Adult male Zucker diabetes fatty rats received Glucophage^® or the generic metformin through gastric gavage at a dose of 180 mg/kg (n = 6 per condition). Both pharmacokinetic parameters (AUC_0–t, AUC_0–∞, C_max) of metformin and plasma glucose levels were compared between the two groups. For pharmacodynamics, rats received Glucophage^® or the generic metformin at doses of 180 and 300 mg·kg^–1·d^–1 for 6 weeks. The measurements included body weight, fasting plasma glucose, glycosylated serum protein (GSP) and serum insulin. Data were analyzed with SPSS 22.0 and Prism 7. The level of statistical significance was set at P<0.05.In single dosing experiments, pharmacokinetic parameters (t_1/2, AUC_0–t and C_max) did not differ between Glucophage^® and the generic metformin (P>0.05). However, plasma glucose was significantly higher in the generic metformin group at 2 h (P = 0.03) and 4 h (P = 0.04) after drug treatment. In repeated dosing experiments, fasting glucose, HOMA-IR and body weight in rats receiving high-dose Glucophage^®were significantly lower at the end of the 6-week treatment period than those in rats receiving high-dose generic metformin (P<0.05 for all). GSP and serum insulin did not differ significantly between the two groups. In rats receiving low-dose metformin, fasting glucose was lower in the Glucophage^® group. HOMA-IR and body weight did not differ between the two groups. Moreover, blood lipids did not differ significantly between the two groups. The generic metformin used in the current study did not differ significantly in pharmacokinetic characteristics with Glucophage^®. However, Glucophage^® was superior in terms of glucose control, body weight loss and insulin sensitivity in repeated administration.

Key words: Metformin, Generic drug, Bioequivalence, Clinical equivalence, Consistency evaluation

CLC Number:

R969.1

Supporting:

Yan Yan, Ling Li, Rui Li, Wenjun Yu, Yi Han, Yukui Ma, Yan Li. Pharmacokinetic and pharmacodynamic comparison between Glucophage? and a generic metformin in a rat model[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(2): 134-142.

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