Indications
Lobeglitazone, a pharmaceutical product approved by the Ministry of Food and Drug Safety in South Korea in 2013, is used under post-marketing surveillance until 2019 for managing diabetes. It is important to note that, as of now, Lobeglitazone has not received approval from major regulatory bodies such as the United States Food and Drug Administration (FDA), Health Canada, or the European Medicines Agency for the treatment of diabetes.
Absorption
In animal studies involving rats, Lobeglitazone exhibited rapid absorption following administration. The area under the curve (AUC) for doses of 0.5, 1, and 2 mg/kg were measured at 459, 514, and 481 µg min/mL, respectively. The time to reach maximum concentration (Tmax) was approximately 67.5 and 48.8 minutes for doses of 0.5 and 2 mg/kg, respectively, with corresponding maximum concentrations (Cmax) of 0.962 and 0.494 µg/mL. Oral administration of Lobeglitazone showed an impressive absolute bioavailability, reported as 92.1% at a 0.5 mg/kg dose and 99.0% at a 2 mg/kg dose. The minimal presence of Lobeglitazone in the gastrointestinal tract 24 hours post-administration suggests near-complete intestinal absorption in the tested dose range.
Metabolism
Metabolic studies conducted on rats indicate that Lobeglitazone is primarily metabolized by cytochrome P450 (CYP) isozymes, particularly CYP2. The primary metabolic pathways include demethylation and hydroxylation. Five major metabolites of Lobeglitazone have been identified, with in vivo studies highlighting the demethylated derivative M1 as the most prominent metabolite. M1 is formed at a rate of approximately 0.216 to 0.252 mL/min/kg, accounting for about 9.76% of the overall elimination of Lobeglitazone in rats. Further investigation is required to fully elucidate the enzymatic processes involved in Lobeglitazone's metabolism.
Mechanism of Action
Lobeglitazone functions as an insulin sensitizer by specifically targeting and activating the Peroxisome Proliferator-Activated Receptor (PPAR) gamma within adipocytes. This activation enhances the binding of insulin in these fat cells, leading to significant reductions in blood glucose levels, decreased hemoglobin A1C (HbA1C) levels, and improvements in lipid profiles and liver function. Unlike Pioglitazone, which acts on both PPAR-alpha and PPAR-gamma, Lobeglitazone is selective for PPAR-gamma, providing a distinctive mechanism of action that may offer specific therapeutic advantages.
