This review article presents the pharmacology of combined Candesartan Cilexetil and Pioglitazone Hydrochloride therapy specially in Metabolic syndrome. Candesartan Cilexetil is a antihypertensive agent. Pioglitazone Hydrochloride is a selectively stimulates nuclear receptor peroxisome proliferator activated receptor gamma (PPAR-gamma). The use of Candesartan Cilexetil in combination with Pioglitazone Hydrochloride has been proved to provide beneficial effect (Synergistic effect) in metabolic syndrome. The mechanism of Candesartan Cilexetil and Pioglitazone Hydrochloride is quite different. The combination of both also have anti inflammatory and enhanced organ protective effects. The main objective of this review article is to provide pharmacological information of combined therapy of Candesartan Cilexetil and Pioglitazone Hydrochloride to researcher in development of combined dosage form of this combination.
I) Insulin resistance
The most accepted hypothesis to describe the pathophysiology of the metabolic syndrome is insulin resistance. That is why the metabolic syndrome is also known as the insulin resistance syndrome. Insulin resistance has been defined as a defect in insulin action that results in hyperinsulinaemia, necessary to maintain euglycaemia. Concept of insulin resistance provides a conceptual framework with which to place a substantial number of apparently unrelated biological events into a pathophysiological construct. A major contributor to the development of insulin resistance is an overabundance of circulating fatty acids, released from an expanded adipose tissue mass. FFA reduce insulin sensitivity in muscle by inhibiting insulin-mediated glucose uptake. Increased level of circulating glucose increases pancreatic insulin secretion resulting in hyperinsulinemia. In the liver, FFA increase the production of glucose, triglycerides and secretion of very low density lipoproteins (VLDL). The consequence is the reduction in glucose transformation to glycogen and increased lipid accumulation in triglyceride (TG). Insulin is an important antilipolytic hormone. In the case of insulin resistance, the increased amount of lipolysis of stored triacylglycerol molecules in adipose tissue produces more fatty acids, which could further inhibit the antilipolytic effect of insulin, creating additional lipolysis.