Rosiglitazone Does Not Alter the Pharmacokinetics of Metformin

Abstract

Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator‐activated nuclear receptor. It improves insulin sensitivity in peripheral tissues and effectively lowers blood glucose in patients with type 2 diabetes. Metformin is a dimethyl‐biguanide, also used in type 2 diabetes, that lowers fasting blood glucose primarily by decreasing hepatic glucose output. Rosiglitazone and metformin reduce plasma glucose concentrations via different mechanisms and thus could potentially be used in combination to optimize glycemic control. This study evaluated the effects of the coadministration of these 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 each for 4 days. Plasma collected on day 4 of each regimen was assayed for rosiglitazone and metformin concentrations. Oral doses of rosiglitazone and metformin were safe and well tolerated when administered alone or in combination. There were no clinically significant episodes of hypoglycemia or increased blood lactic acid levels following treatment with any regimen. Coadministration of rosiglitazone and metformin had no significant effects on the steady‐state pharmacokinetics (AUC(0‐12h), Cmax, tmax, or t1/2) of either drug. The authors conclude that rosiglitazone can be safely administered 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.

Rosiglitazona

“…No se han demostrado efectos clínicamente relevantes en la farmacocinética de nifedipino o de los anticonceptivos orales, los cuales son metabolizados principalmente por CYP3A4 (28-30), digoxina (31) o ranitidina (32).…”

Rosiglitazone

“…These changes are not believed to be clinically significant; therefore, rosiglitazone may be administered in the fed or fasting state. Pharmacokinetic studies of rosiglitazone in combination with acarbose 17 and metformin 48 revealed no significant interactions with these commonly used antidiabetic agents. The pharmacokinetics of rosiglitazone were also unaltered by pretreatment with ranitidine, indicating that oral rosiglitazone is not affected by increases in gastrointestinal pH 49,50…”