Actos Clinical Pharmacology

Drug Library
Actos - Clinical Pharmacology [Pioglitazone]

Ketoconazole:

Co-administration of ACTOS for 7 days with ketoconazole 200 mg adminis-tered twice daily resulted in least square mean (90% Cl) values for unchanged pioglitazone of 1.14 (1.06 -1.23) for Cmax, 1.34 (1.26 -1.41) for AUC and 1.87 (1.71 -2.04) for Cmin. Atorvastatin Calcium: Co-administration of ACTOS for 7 days with atorvastatin calcium (LIPITOR Ž ) 80 mg once daily resulted in least square mean (90% Cl) values for unchanged pioglitazone of 0.69 (0.57 -0.85) for Cmax, 0.76 (0.65 -0.88) for AUC and 0.96 (0.87 -1.05) for Cmin. For unchanged atorvastatin the least square mean (90% Cl) values were 0.77 (0.66 -0.90) for Cmax, 0.86 (0.78 -0.94) for AUC and 0.92 (0.82 -1.02) for Cmin.

Theophylline:
Co-administration of ACTOS for 7 days with theophylline 400 mg adminis-tered twice daily resulted in no change in the pharmacokinetics of either drug. Oral Contraceptives: See PRECAUTIONS. Cytochrome P450: See PRECAUTIONS.

Pharmacodynamics and Clinical Effects

Clinical studies demonstrate that ACTOS improves insulin sensitivity in insulin-resistant patients. ACTOS enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, improves hepatic sensitivity to insulin, and improves dysfunctional glucose homeostasis.

In patients with type 2 diabetes, the decreased insulin resistance pro-CH3 duced by ACTOS results in lower blood glucose concentrations, lower plasma insulin levels, and lower HbA1c values. Based on results from an open-label extension study, the glucose lowering effects of ACTOS appear to persist for at least one year. In controlled clinical trials, ACTOS in combination with sulfonylurea, metformin, or insulin had an addi-tive effect on glycemic control.

Patients with lipid abnormalities were included in clinical trials with ACTOS. Overall, patients treated with ACTOS had mean decreases in triglycerides, mean increases in HDL cholesterol, and no consistent mean changes in LDL and total cholesterol. In a 26-week, placebo-controlled, dose-ranging study, mean triglyceride levels decreased in the 15 mg, 30 mg, and 45 mg ACTOS dose groups compared to a mean increase in the placebo group. Mean HDL levels increased to a greater extent in patients treated with ACTOS than in the placebo-treated patients. There were no consistent differences for LDL and total cholesterol in patients treated with ACTOS compared to placebo (Table 1).