Placental transfer of rosiglitazone in the ex vivo human perfusion model

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 14 C-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.