Pioglitazone Hcl (pioglitazone HCl)

Pioglitazone, a thiazolidinedione (glitazone), is an antidiabetic agent.

Pioglitazone is a thiazolidinedione (glitazone) antidiabetic agent that is structurally and pharmacologically related to troglitazone and rosiglitazone but unrelated to other antidiabetic agents, including sulfonylureas, biguanides, and alpha-glucosidase inhibitors.

Pioglitazone acts principally by increasing insulin sensitivity in target tissues, as well as decreasing hepatic gluconeogenesis. Pioglitazone is a peroxisome proliferator-activated receptorgamma (PPARgamma) agonist that increases transcription of insulin-responsive genes and increases insulin sensitivity. Pioglitazone ameliorates insulin resistance associated with type 2 diabetes mellitus without stimulating insulin release from pancreatic beta cells, thus avoiding the risk of hypoglycemia.

Because pioglitazone does not lower glucose concentrations below euglycemia, the drug is appropriately referred to as an antidiabetic agent rather than a hypoglycemic agent. Some evidence suggests that the glucoregulatory effects of thiazolidinediones are mediated in part via enhanced hepatic and peripheral glucose uptake and reduced systemic and tissue lipid availability.

Following oral administration of pioglitazone, peak plasma concentrations are achieved within 2 hours. Food delays time to peak concentrations to 3-4 hours but does not alter AUC. Pioglitazone is extensively (>99%) protein bound, principally to serum albumin.

Pioglitazone is extensively metabolized via hydroxylation and oxidation, principally via the cytochrome P-450 (CYP) 2C8 and CYP3A4 isoenzymes, with involvement of several other isoforms, including CYP1A1 (mainly an extrahepatic isoenzyme). The major circulating active metabolites of pioglitazone are M-III (keto derivative) and M-IV (hydroxyl derivative). Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine.

Renal elimination 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 is eliminated in the feces. The mean serum half-life of pioglitazone and its metabolites (M-III and M-IV) range from 3 to 7 hours and 16 to 24 hours, respectively.

The serum elimination half-life of pioglitazone and metabolites remains unchanged in patients with moderate (creatinine clearance 30--50 mL/minute) and severe (creatinine clearance <30 mL/minute) renal impairment when compared to subjects with normal renal function. Compared with healthy controls, subjects with impaired hepatic function (Child-Pugh class B and C) have an approximate 45% reduction in pioglitazone and total pioglitazone (pioglitazone, M-III, M-IV) mean peak plasma concentration but no change in the mean AUC values. In healthy elderly subjects, mean peak plasma concentration was not significantly different, but AUC values were approximately 21% higher than those achieved in younger subjects; the mean half-life was also prolonged (10 hours) compared to younger subjects (7 hours).

These changes observed in elderly subjects is not considered clinically relevant. The mean peak plasma concentration and AUC values of pioglitazone were increased 20% to 60% in women compared to men.

Bioequivalence has been demonstrated between the fixed combination of pioglitazone and immediate-release metformin hydrochloride and each agent given concurrently as separate tablets at the currently approved dosage strengths (500 or 850 mg of metformin hydrochloride and 15 mg of pioglitazone). Bioequivalence also has been demonstrated between the fixed combination of pioglitazone and glimepiride and each agent given concurrently as separate tablets at the currently approved dosage strengths (2 or 4 mg of glimepiride and 30 mg of pioglitazone).

USES: Pioglitazone is a diabetes drug (thiazolidinedione-type, also called "glitazones") used along with a proper diet and exercise program to control high blood sugar in patients with type 2 diabetes. It works by helping to restore your body's proper response to insulin, thereby lowering your blood sugar. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems.

Proper control of diabetes may also lessen your risk of a heart attack or stroke.

Generic name: pioglitazone HCl
Pronunciation: (PYE-oh-GLI-ta-zone)

The following indications are listed for Pioglitazone Hcl:

• Type 2 Diabetes Mellitus

Also known as: Adult Onset Diabetes, Adult Onset Diabetes Mellitus, Adult Onset Dm, Diabetes Mellitus Type 2, Diabetes Mellitus Type Ii, Ketosis-Resistant Diabetes Mellitus, Ketosis-Resistant Dm, Maturity Onset Diabetes, Maturity Onset Diabetes Mellitus, Non-Insulin Dependent Diabetes Mellitus, Non-Insulin-Dependent Diabetes Mellitus, Type Ii Diabetes Mellitus.

No ICD codes are available for this drug.