This study aimed to investigate the bioequivalence of 2 formulations of gliclazide modified-release tablets 60 mg in 48 healthy Caucasian volunteers under fasting conditions. A test product, Gliclazide MR (Ranbaxy Laboratories Limited, now Sun Pharmaceutical Industries, India), was compared with a reference product, Diamicron MR (Servier, France). The study was performed under a single-dose, 2-treatment, 2-period, 2-sequence crossover design in a fasted condition with a washout period of 21 days. Blood samples were collected for 96 hours after drug administration. Drug plasma concentrations were determined by a liquid chromatography-tandem mass spectrometry method. Analysis of pharmacokinetic characteristics was based on a noncompartmental model. The logarithmically transformed data of C and AUC were analyzed for 90% confidence intervals using analysis of variance. There was no significant difference in pharmacokinetic characteristics between the products, and the 90% confidence intervals were within the acceptance range of 80.00%-125.00%. The investigated products were bioequivalent under fasted conditions.

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Objective: To evaluate the food effect on glicazide disposition in clinical trials conducted on healthy Caucasian volunteers who were given a new modified release oral formulation of Gliclazide 60 mg developed by Sun Pharmaceutical Industries, India.Methods: The studies were designed as open-label, randomized, single-dose, crossover studies that consisted of two periods. During each study, venous blood samples were taken before and after drug administration up to 96 hours. Subsequently, individual plasma profiles were determined and non-compartmental method was employed for the assessment of food effect on the pharmacokinetic profile of gliclazide. The statistical significance of differences for the main pharmacokinetic parameters was evaluated by ANOVA test, for p < 0.05 statistical significance was decided. The relative profiles of absorption of gliclazide were obtained by mathematical deconvolution. All calculation were performed by Phoenix WinNonlin®.Results: High-fat, high-calorie meal decreased gliclazide exposure. The mean maximum plasma concentration decreased with 14%, while the mean total area under the plasma concentration-time profile registered a 17% decrease. The elimination half-lives under fasted and fed conditions were comparable and the time to maximum plasma concentration was shortened under fed condition. Safety evaluation showed that overall gliclazide was well tolerated under both fasted and fed condition.Conclusions: The statistical analysis revealed the lack of food effect on the new modified release tablets of Gliclazide 60 mg. However, before stating a definite conclusion regarding the food effect on gliclazide pharmacokinetic profile, additional studies on patients with type 2 diabetes mellitus should be conducted.

The present study aimed to elucidate and describe the basic pharmacokinetics of dapagliflozin after a single dose oral administration of a 10 mg immediate release tablet developed by Sun Pharmaceutical Industries Limited, India. Ten competing models were created in order to analyze the experimental data obtained from the 71 subjects who were enrolled and finalized two bioequivalence clinical trials, under fasting and fed state. The studies took place at the Clinical Pharmacology and Pharmacokinetics Department of Terapia S.A. Considering the Akaike index value for a rational model discrimination, model number 8 (M8) was found to be the best that fits the experimental data. The representative pharmacokinetic model involves zero order absorption kinetics with a lag time of approximately 0.3 hours, first order systemic metabolism and elimination and two-compartmental distribution. Furthermore, by using M8, the most important pharmacokinetic parameters of dapagliflozin were determined. All calculations were performed by Phoenix WinNonlin ® version 6.3 (Certara, USA).

Objective: The aim of the present study was to evaluate the relative bioavailability of two formulations containing 10 mg dapagliflozin in healthy Caucasian subjects under fasting conditions.Materials and Methods: Forty-eight healthy Caucasian subjects were enrolled in a single-dose, crossover, balanced, open label, randomized clinical trial, with two treatment, two periods and two sequences. The wash-out period was of 7 days and thirty-eight subjects completed both study periods. Each subject received a single dose of 10 mg dapagliflozin as the reference product Farxiga® (AstraZeneca Pharmaceuticals LP, USA) and the test product developed by Sun Pharmaceutical Industries, India. Dapagliflozin plasma levels were determined from blood samples collected in both study periods before and after dosing until 48 hours by using a validated LC-MS/MS method. For pharmacokinetic analysis of data, the non-compartmental method was used (Phoenix® WinNonlin 6.3). The statistical analysis was performed by SAS software 9.1.3 for the logarithmically transformed values of maximum plasma concentration and area under the curve.Results: The 90% confidence intervals for the evaluated pharmacokinetic parameters were found to be in the accepted interval for bioequivalence (80.00-125.00%).Conclusion: The 10 mg dapagliflozin immediate release tablet newly developed by Sun Pharmaceutical Industries, India, is bioequivalent with the reference product Farxiga® under fasted state of the subjects.