Interaction of p-synephrine on the pharmacodynamics and pharmacokinetics of gliclazide in animal models

BACKGROUND: Type 2 diabetes is frequently seen in patients suffering from obesity. p-synephrine and gliclazide are widely used medicines for the treatment of obesity and diabetes, respectively. OBJECTIVES: The present study was undertaken to determine the potential for interactions between p-synephrine and gliclazide, based on the relationship between obesity and diabetes. METHODS: Influence of p-synephrine on the activity of gliclazide was determined by conducting single and multiple dose interaction studies in animal models. Blood samples collected at pre-determined time intervals from experimental animals were used for the estimation of glucose and insulin levels. The insulin resistance and β-cell function were determined by homeostasis model assessment. Additionally, serum gliclazide levels in rabbits were analyzed by high-performance liquid chromatography (HPLC). RESULTS: Gliclazide alone showed peak reduction in blood glucose levels at 2 and 8 h after administration in rats and after 3 h in rabbits. The activity of gliclazide was not altered by a single dose treatment with p-synephrine. However, in multiple dose interaction studies, samples from all the time points analyzed showed significant changes in percent blood glucose reduction ranging from 19.73 to 44.18% in normal rats, 23.76–46.43% in diabetic rats and 16.36–38.34% in normal rabbits. The homeostasis model assessment parameters were also significantly altered in multiple dose interaction studies. The pharmacokinetics of gliclazide was not altered by either single or multiple dose p-synephrine treatments in rabbits. CONCLUSION: The effect of multiple dose p-synephrine treatments upon gliclazide appeared to be pharmacodynamic in nature, indicating the need for periodic monitoring of glucose levels and dose adjustment as necessary when this combination is prescribed to obese patients.