title: Evaluation of developmental toxicity of propylthiouracil and methimazole.
abstract: BACKGROUND
  Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs.
  
  
  METHODS
  We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20.
  
  
  RESULTS
  In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed.
  
  
  CONCLUSIONS
  We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy.
authors: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida.
authors: Murali K
authors: MK
authors: Mallela
authors: Marie
authors: M
authors: Strobl
authors: Ryan R
authors: RR
authors: Poulsen
authors: Christopher C
authors: CC
authors: Wendler
authors: Carmen J
authors: CJ
authors: Booth
authors: Scott A
authors: SA
authors: Rivkees
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006980:Hyperthyroidism / Q000188:drug therapy*; D008713:Methimazole / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced*; D011441:Propylthiouracil / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity
chemical_list: D013956:Antithyroid Agents; D013723:Teratogens; D008713:Methimazole; D011441:Propylthiouracil
keywords: antithyroid drugs; developmental toxicity; methimazole; propylthiouracil