期刊
REPRODUCTIVE TOXICOLOGY
卷 61, 期 -, 页码 162-168出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2016.04.008
关键词
Drug disposition; Trans-placental; Non-placental; Pregnant ewe
资金
- Career Development Award from National Health and Medical Research Council of Australia (NHMRC) [APP1004211]
- South Australian Cardiovascular Research Network Fellowship [CR10A4988]
- NHMRC CDF [APP1066916]
- NHMRC Project Grant [456425]
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 similar to 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 similar to 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. (C) 2016 Elsevier Inc. All rights reserved.
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