Limited fetal metabolism of rosiglitazone: Elimination via the maternal compartment in the pregnant ewe

Maryam Bazargan, David J.R. Foster, Beverly S. Muhlhausler, Janna L. Morrison, ICaroline McMillen, Andrew K. Davey

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalReproductive Toxicology
Publication statusPublished or Issued - 1 Jun 2016
Externally publishedYes


  • Drug disposition
  • Non-placental
  • Pregnant ewe
  • Trans-placental

ASJC Scopus subject areas

  • Toxicology

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