Effect of fucoxanthin on the pharmacodynamics and pharmacokinetics of gliclazide in animal models

2016-12-12T10-17-34Z
Source: Journal of Experimental and Integrative Medicine
LEELA KRISHNA VATSAVAI, ESWAR KUMAR KILARI.
Objective: Type 2 diabetes may occur in patients suffering from obesity. Gliclazide is the most commonly used drug of choice for the treatment of type 2 diabetes and fucoxanthin is widely used for the management of obesity. As these two drugs intersect at a point, it is essential to investigate the effect of oral administration of fucoxanthin on the pharmacodynamics and pharmacokinetics of gliclazide in animal models to further evaluate the safety and effectiveness of this combination. Methods: Influence of fucoxanthin on the activity of gliclazide was determined by conducting single and multiple dose interaction studies in rats (normal and diabetic) and rabbits. Blood samples collected at pre-determined time intervals were used for the estimation of glucose and insulin levels by using automated clinical chemistry analyzer and radio immune assay methods, respectively. 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. Results: Administration of gliclazide resulted in peak reduced blood glucose levels at 2 h and 8 h in rats and at 3 h in rabbits. This activity of gliclazide was not altered by single dose treatment with fucoxanthin. However, multiple dose interaction study of fucoxanthin with gliclazide resulted in significantly greater reduction in blood glucose levels ranging from 22.27 to 45.81% in normal rats, 28.45 to 44.68% in diabetic rats and 15.01 to 40.72% in rabbits. This observation was coupled with significantly increased insulin level, β-cell function and insulin resistance index in animal models. The pharmacokinetics of gliclazide in rabbits was significantly altered by repeated dose treatments of fucoxanthin and the percent increase in serum gliclazide concentration was found to be 13.93 % when compared to gliclazide control. Conclusion: From this study it is concluded that the interaction of fucoxanthin with gliclazide upon multiple dose treatments is pharmacokinetic in nature. This combination when prescribed/taken for clinical use in obese patients requires dose adjustments and periodic monitoring of blood glucose levels.


http://ift.tt/2hqw7HA