PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF MANGOSTEEN EXTRACT (GARCINIA MANGOSTANA L) WITH GLICLAZIDE AND METFORMIN IN DIABETIC RATS

• Main Author: Mirawati
• Format: Dissertations
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/48951
• Institution: Institut Teknologi Bandung

Currently, the use of herbs as a complement or alternative medicine is increasingly popular around the world. Herbs are often given in combination with a therapeutic drug that has the potential to cause drug-herbal interactions. Several studies have demonstrated the benefits of herbs as a complement to therapeutic drugs, including in the treatment of diabetes mellitus (DM). Diabetes mellitus is a metabolic disorder with a high prevalence and based on reports from WHO, DM was the cause of death of 1.6 million people worldwide in 2015. Mangosteen pericarp is one of the herbs that have an antihyperglycemic effect. The use of mangosteen extract (EM) in the treatment of diabetes mellitus has required information on its efficacy, safety, and interaction that occurs when administered together with oral antihyperglycemic drugs. The possible interactions are pharmacokinetic and pharmacodynamic interactions. This study aims to determine the pharmacokinetic and pharmacodynamic interactions between mangosteen extract with the oral antihyperglycemic drug in DM rats and to know the mechanism of interaction that occurred. AM which is the most abundant xanton in the mangosteen pericarp and also has an effect as antihyperglycemic is used as a marker. The study was conducted on three animal models: normoglycemia, DM rats with alloxan induction (DMIA) and DM rats with insulin resistant (DMRI). Oral antihyperglycemic drugs used were gliclazide (GK) and metformin (MFN). Pharmacokinetic interactions are determined by comparing the pharmacokinetic profiles and parameters of single and concomitant administration. While pharmacodynamic interactions were determined by comparing the percent decrease in blood glucose and pharmacodynamic-pharmacokinetic relationship curves. Pharmacokinetic profiles and parameters were determined by analysis of levels of gliclazide, metformin and alpha mangostin in plasma using HPLC. The effect of glucose decrease was determined by the GOD-PAP method. The pharmacokinetic profile of gliclazide follows the oral model of two compartments in both normal and DMIA rats. Similarly, single and combination administration with AM and EM. Absorption and distribution of gliclazide in normal rats were influenced by AM and EM but not in DMIA rats. The values of ? and Ka decreased significantly (p <0.05), values of t1/2?, t max, Vd?, Cl, and AUC increased significantly (p <0.05). Side effects (hypoglycemic) were eliminated and the antihyperglycemic effect of gliclazide decreased with AM and EM Metformin had a pharmacokinetic profile following the two-compartment oral model. This profile was unchanged by combination with AM and EM as well as on the conditions of DMIA rats. However, in DMRI rats showed a double peak in combination with EM. DM conditions increase the bioavailability of metformin by two-fold compared to normal conditions. AM and EM increased t1/2?from metformin in normal and DMRI rats. Whereas in DMIA rats, EM increased distribution and clearance, so AUC decreased significantly (p <0.05). AM and EM increased the total antihyperglycemic effect of metformin (based on AAC) in both normal, DMIA and DMRI rats. The onset of action of metformin was accelerated in DMIA rats and increased of duration effect in DMRI rats. The pharmacokinetic AM profile after a single administration and EM was unchanged in normal, DMIA and DMRI rats, as well as on combination administration with gliclazide and metformin. Co-administration of metformin and AM/EM affects the elimination of AM in DMIA rats. AM has potent antihyperglycemic effects both in normal and DMIA rats. While EM has no antihyperglycemic effect on normal rats and has a low antihyperglycemic effect on DMIA and DMRI rats. This study yields data on pharmacokinetic and pharmacodynamic interactions of AM and EM with oral antihyperglycemic drugs under normal conditions, DMIA and DMRI. The combination of AM and EM with gliclazide is less beneficial than the combination of AM or EM with metformin. AM can be an alternative medicine in DM treatment especially if its bioavailability can be improved. EM can only be used as a complement drug especially with metformin because it increases the effect and accelerates metformin action. This study yields data on pharmacokinetic and pharmacodynamic interactions of AM and EM with oral antihyperglycemic drugs under normal, DMIA and DMRI conditions. The combination of AM and EM with gliclazide is less beneficial than the combination of AM or EM with metformin. AM can be an alternative medicine in DM treatment especially if its bioavailability can be improved. EM can only be used as a complement drug especially with metformin because it increased the effect and accelerated metformin action.