Pharmacokinetics and clinical efficacy of pioglitazone.

Pioglitazone is a thiazolidinedione that increases insulin sensitivity in target tissues. It is well-absorbed, with a mean absolute bioavailability of 83% and reaching maximum concentrations in around 1.5 hours. It is metabolised by the hepatic cytochrome P450 enzyme system. However, unlike troglitazone, studies have provided no evidence to suggest that pioglitazone administration leads to inhibition or induction of any of the P450 isoenzymes involved in drug metabolism. Therefore pioglitazone may have lower potential for drug interaction. The half-life is about 9 hours but two active metabolites mainly contribute to the extended glucose-lowering effects. It is administered once daily without regard to meals. The pharmacokinetics are not significantly altered in Type 2 diabetes, renal or hepatic insufficiency or in the elderly. In placebo-controlled clinical studies, pioglitazone effectively improved glycaemic control in people with Type 2 diabetes as evidenced by significant reductions in HbA1c and fasting plasma glucose, whether used as monotherapy or in combination with sulphonylurea, metformin or insulin. Pioglitazone also had a beneficial effect on the abnormal lipid profile seen in Type 2 diabetes. Compared with placebo, pioglitazone significantly reduced serum triglycerides and increased high density lipoprotein cholesterol with no change in low density lipoprotein or total cholesterol.