Objective: The objective of the study was to determine transplacental passage of rosiglitazone (Avandia) using the ex vivo human placental model. Study design: Perfusion studies were performed on 10 placentas from term, uncomplicated deliveries. Concentrations typical for an 8-mg oral dose (216 to 692 ng/mL) as well as 2- to 3-fold increased concentrations were tested (734 to 1261 ng/mL). Transfer of rosiglitazone was assessed and accumulation was determined using the 14C-antipyrine reference method. Results: The clearance index for low and high concentrations were 0.14 ± 0.04 and 0.20 ± 0.08, suggesting that the drug passes through the placenta at a relatively low rate. Fetal accumulation occurred in only 1 of 5 placentas at 16.4 ng/mL (5%) for the 8-mg dose and in 2 of 5 placentas ranging from 0 to 74 ng/mL (5% to 8%) at higher concentrations. Conclusion: There is minimal transfer and fetal accumulation of rosiglitazone according to the ex vivo human perfusion model. © 2006 Mosby, Inc. All rights reserved.