Rosiglitazone does not alter the pharmacokinetics of metformin

Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activate d nuclear receptor. It improves insulin sensitivity in peripheral tissues a nd effectively lowers blood glucose in patients with type 2 diabetes. Metfo rmin is a dimethyl- biguanide, also used in type 2 diabetes, that lowers fa sting blood glucose primarily by decreasing hepatic glucose output. Rosigli tazone and metformin reduce plasma glucose concentrations via different mec hanisms and thus could potentially be used in combination to optimize glyce mic control. This study evaluated the effects of the coadministration of th ese two agents on the pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers (22-55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone (2 mg every 12 hours), or the combination ea ch for 4 days. Plasma collected on day 4 of each regimen was assayed for ro siglitazone and metformin concentrations. Oral doses of rosiglitazone and m etformin were safe and well tolerated when administered alone or in combina tion. There were no clinically significant episodes of hypoglycemia or incr eased blood lactic acid levels following treatment with any regimen. Coadmi nistration of rosiglitazone and metformin had no significant effects on the steady-state pharmacokinetics (AUC((0-12h)), C-max, t(max), Or t(1/2)) of either drug. The authors conclude that rosiglitazone can be safely administ ered with metformin and, due to the different mechanisms of action of these agents, may offer a therapeutic advantage in patients with type 2 diabetes mellitus. (C) 2000 the American College of Clinical Pharmacology.