title: Methimazole and propylthiouracil equally cross the perfused human term placental lobule.
abstract: Propylthiouracil (PTU) is widely believed to cross the placenta less freely than methimazole (MMI) and is therefore regarded as the preferred drug for treatment of hyperthyroidism in pregnancy. Clinical studies comparing the two drugs show, however, no differences in maternal or fetal thyroid function. We investigated transfer from the maternal to the fetal circuit in the isolated perfused term human placental lobule of low and high doses of PTU (4 micrograms/mL and 40 micrograms/mL) and MMI (1.5 micrograms/mL and 15 micrograms/mL) in protein-free perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin. Both drugs readily crossed the placenta, reaching equilibrium in all experiments in about 2 h. Drug concentrations in the two circuits fitted a two compartmental model. Transfer kinetics for the two drugs were similar, nonsaturable, and unaffected by addition of albumin. Clearances (mL.min-1.g-1, means +/- SD) of PTU from maternal to fetal circuits were: 0.229 +/- 0.110, 0.216 +/- 0.065, and 0.170 +/- 0.032; and for transfer of MMI: 0.165 +/- 0.025, 0.232 +/- 0.153, and 0.174 +/- 0.009 (for low doses without, low doses with, and high doses without albumin, respectively). Clearances of PTU from fetal to maternal circuits were: 0.147 +/- 0.072, 0.109 +/- 0.014, and 0.116 +/- 0.028; and for transfer of MMI: 0.095 +/- 0.029, 0.122 +/- 0.088, and 0.12 +/- 0.005 (in the same experiments). There was no significant difference between drugs or drug doses and no effect of addition of albumin. We conclude that PTU and MMI have similar placental transfer kinetics.
authors.affiliation: Conjoint Endocrine Laboratory, Royal Brisbane Hospital, Australia.
authors.forename: R H
authors.initials: RH
authors.lastname: Mortimer
authors.forename: G R
authors.initials: GR
authors.lastname: Cannell
authors.forename: R S
authors.initials: RS
authors.lastname: Addison
authors.forename: L P
authors.initials: LP
authors.lastname: Johnson
authors.forename: M S
authors.initials: MS
authors.lastname: Roberts
authors.forename: I
authors.initials: I
authors.lastname: Bernus
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000493:pharmacokinetics*; D036861:Delivery, Obstetric; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D008713:Methimazole / Q000493:pharmacokinetics*; D008954:Models, Biological; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011441:Propylthiouracil / Q000493:pharmacokinetics*; D012709:Serum Albumin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D013956:Antithyroid Agents; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D008713:Methimazole; D011441:Propylthiouracil