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.


METHODS
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.


CONCLUSIONS
There is minimal transfer and fetal accumulation of rosiglitazone according to the ex vivo human perfusion model.
Holmes
Heather J
HJ
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Casey
Brian M
BM
Bawdon
Roger E
RE
D000284:Administration, Oral; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008954:Models, Biological; D009994:Osmolar Concentration; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone