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Treatment of Type II diabetes mellitus
Pioglitazone acts as an agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors increases the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, pioglitazone both enhances tissue sensitivity to insulin and reduces hepatic gluconeogenesis. Thus, insulin resistance associated with type 2 diabetes mellitus is improved without an increase in insulin secretion by pancreatic β cells.
Hypogycemia; LD<sub>50</sub>=mg/kg (orally in rat)
Following oral administration, in the fasting state, pioglitazone is first measurable in serum within 30 minutes, with peak concentrations observed within 2 hours. Food slightly delays the time to peak serum concentration to 3 to 4 hours, but does not alter the extent of absorption.
3-7 hours
Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces.
* 0.63 ± 0.41 L/kg
* apparent cl=5 - 7 L/h [oral administration]