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.
4. Chen X-W He Z-X Zhou Z-W Yang T Zhang X Yang Y-X Duan W Zhou S-F. Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus. Clin Exp Pharmacol P. 2015;42:999-1024.
5. Verspohl EJ. Novel pharmacological approaches to the treatment of type 2 diabetes. Pharmacol Rev. 2012;64:188-237.
6. He Z-X Zhou Z-W Yang Y Yang T Pan S-Y Qiu J-X Zhou S-F. Overview of clinically approved oral antidiabetic agents for the treatment of type 2 diabetes mellitus. Clin Exp Pharmacol P. 2015;42:125-38.
7. Blonde L San Juan ZT. Fixed-dose combinations for treatment of type 2 diabetes mellitus. Adv Ther. 2012;29(1):1-13.
8. Hays NP Galassetti PR Coker RH. Prevention and treatment of type 2 diabetes: current role of lifestyle natural product and pharmacological interventions. Pharmacol Ther. 2008;118(2):181-91.
9. Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014 Jun;13(6):465-76.
10. Garber A et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2017 executive summary. Endocr Pract. 2017;23(2):207-38.
11. Sarkar A Tiwari A Bhasin PS Mitra M. Pharmacological and pharmaceutical profile of gliclazide: a review. J Appl Pharm Sci. 2011;01(09):11-9.
12. Alsharidah M Algeffari M Abdel-Moneim H Lutfi MF Alshelowi H. Effect of combined gliclazide/metformin treatment on oxidative stress lipid profile and hepatorenal functions in type 2 diabetic patients. Saudi Pharm J. 2018;26:1-6.
13. Landman GWD de Bock GH van Hateren KJJ van Dijk PR Groenier KH et al. Safety and efficacy of gliclazide as treatment for type 2 diabetes: a systematic review and meta-analysis of randomized trials. PLoS ONE. 2014;9(2):e82880. doi:10.1371/journal.pone.0082880.
14. Elliot DJ Suharjono Lewis BC et al. Identification of the human cytochromes P450 catalyzing the rate-limiting pathways of gliclazide elimination. Br J Clin Pharmacol. 2007;64(4):450-7.
15. Todor I Muntean D Neag M et al. The influence of CYP2D6 phenotype on the pharmacokinetic profile of atomoxetine in Caucasian healthy subjects. Acta Medica Marisiensis. 2017;63(2):73-9.
16. Rojanasthien N Autsavakitipong T Kumsorn B et al. Bioequivalence study of modified-release Gliclazide tablets in healthy volunteers. ISRN Pharmacol. 2012;2012. doi:10.5402/2012/375134.
17. Gilroy CA Luginbuhl KM Chilkoti A. Controlled release of biologics for the treatment of type 2 diabetes. J Control Release. 2016;240:151-64.
19. Pop DI Oroian M Bhardwaj S Marcovici A Khuroo A Kochhar R Vlase L. Bioequivalence of two formulations of gliclazide in a randomized crossover study in healthy Caucasian subjects under fasting conditions. Clin Pharm Drug Dev. 2018. doi: 10.1002/cpdd.445.
20. Guidance for industry. Food-effect Bioavailability and Fed Bioequivalence Studies. 2002. Available at:https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070241.pdf
21. European Medicines Agency. Guideline on the investigation of drug interactions. 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf.
22. Guidelines for bioavailability and bioequivalence studies. Central Drugs Standard Control Organization Government of India New Delhi. 2005. Available at: http://www.cdsco.nic.in/html/BE%20Guidelines%20Draft%20Ver10%20March%2016,%2005.pdf
23. Grbic S Parojcic J Ibric S Djuric Z. In vitro-In vivo correlation for gliclazide immediate-release tablets based on mechanistic absorption simulation. AAPS Pharm Sci Tech. 2011;12(1):165-71.
24. Davis TME Daly F Walsh JP Ilett KF Beilby JP Dusci LJ Barrett PHR. Pharmacokinetics and pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2 diabetes. Br J Clin Pharmacol. 2000;49(3):223-30.