TY - JOUR
T1 - Limited fetal metabolism of rosiglitazone: elimination via the maternal compartment in the pregnant ewe
AU - Bazargan, Maryam
AU - Foster, David
AU - Muhlhausler, Beverly
AU - Morrison, Janna
AU - McMillen, ICaroline
AU - Davey, Andrew
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Despite the fact that fetal drug exposure is common, the disposition of drugs in the fetus is poorly understood. This study aimed to investigate fetal placental and non-placental disposition of rosiglitazone in the pregnant ewe. Steady state was reached after day 5 of fetal infusion, and were ~1.8 fold higher than maternal concentrations (P < 0.001). The AUC for fetal rosiglitazone concentration throughout the infusion was inversely correlated with placental and fetal weight. Metabolic activity of the fetal liver microsomes were ~25 fold lower than maternal microsomes (P < 0.001). The findings suggest that trans-placental transfer is the major route through which rosiglitazone is cleared from the fetal compartment, while non-placental hepatic elimination makes only a minor contribution. This supports a limited capacity of the fetus for eliminating this class of drugs, and highlights the potential for drug toxicity when administering pharmacotherapy to the mother/fetus in human pregnancy.
AB - Despite the fact that fetal drug exposure is common, the disposition of drugs in the fetus is poorly understood. This study aimed to investigate fetal placental and non-placental disposition of rosiglitazone in the pregnant ewe. Steady state was reached after day 5 of fetal infusion, and were ~1.8 fold higher than maternal concentrations (P < 0.001). The AUC for fetal rosiglitazone concentration throughout the infusion was inversely correlated with placental and fetal weight. Metabolic activity of the fetal liver microsomes were ~25 fold lower than maternal microsomes (P < 0.001). The findings suggest that trans-placental transfer is the major route through which rosiglitazone is cleared from the fetal compartment, while non-placental hepatic elimination makes only a minor contribution. This supports a limited capacity of the fetus for eliminating this class of drugs, and highlights the potential for drug toxicity when administering pharmacotherapy to the mother/fetus in human pregnancy.
KW - Drug disposition
KW - Non-placental
KW - Pregnant ewe
KW - Trans-placental
UR - http://www.scopus.com/inward/record.url?scp=84962854203&partnerID=8YFLogxK
U2 - 10.1016/j.reprotox.2016.04.008
DO - 10.1016/j.reprotox.2016.04.008
M3 - Article
VL - 61
SP - 162
EP - 168
JO - Reproductive Toxicology
JF - Reproductive Toxicology
SN - 0890-6238
ER -