Pio-LN Mechanism of Action

Pharmacology: Pioglitazone lowers insulin resistance by activating nuclear receptors (peroxisome proliferator-activated receptor-gamma), increase insulin sensitivity in the liver, adipose tissue and skeletal muscle cells. In the case of insulin resistance, pioglitazone lowers glucose production in the liver and increasing glucose uptake in peripheral tissues. Fasting plasma glucose and postprandial improved in patients with type 2 diabetes blood sugar control improvements related to plasma insulin concentrations both when fasting and postprandial. Pioglitazone did not affect the function of pancreatic β cells.
Pharmacokinetics: Pioglitazone rapidly adsorbed after oral administration. Peak levels achieved 2 hours after administration. Repeat dosing did not lead to accumulation. Absolute bioavailability >80%.
Pioglitazone and its metabolites bind strongly to plasma protein (>99%).
Pioglitazone is metabolized in the liver by hydroxylation of aliphatic methylene groups, primarily through the cytochrome P-450 2C9 and 3A4. 3 of 6 metabolites are active (M-II, M-III, and M-IV).
Pioglitazone excreted through feces and urine.
Pioglitazone half time 5-6 hours and its metabolites 16-23 hours, but the volume of distribution increases and decreases intrinsic clearance.
Patients with impaired renal function: Pioglitazone and metabolic concentrations were lower in patients with impaired renal function compared with patients with normal kidney function.
Patients with impaired hepatic function: Pioglitazone plasma concentrations did not change but the volume of distribution increases and decreases intrinsic clearance.