| Indication |
Treatment of Type II diabetes mellitus |
| Pharmacodynamics |
Pioglitazone, a member of the drug group known as the
thiazolidinediones or "insulin sensitizers", is not chemically or
functionally related to the alpha-glucosidase inhibitors, the
biguanides, or the sulfonylureas. Pioglitazone targets insulin
resistance and, hence, is used alone or in combination with insulin,
metformin, or asulfonylurea as an antidiabetic agent. |
| Mechanism of action |
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. |
| Absorption |
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. |
| Volume of distribution |
|
| Protein binding |
> 99% |
| Metabolism |
Hepatic |
| Route of elimination |
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. |
| Half life |
3-7 hours |
| Clearance |
- apparent cl=5 – 7 L/h [oral administration]
|
| Toxicity |
Hypogycemia; LD50=mg/kg (orally in rat) |
