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Methimazole and Propylthiouracil Equally Cross the Perfused Human Term Placental Lobule¹

Conjoint Endocrine Laboratory (R.H.M., G.R.C., R.S.A., I.B.) and Division of Chemical Pathology (G.R.C., L.P.J., I.B.), Royal Brisbane Hospital, Australia, Q4029; and Departments of Obstetrics and Gynaecology (R.H.M.) and Medicine (M.S.R.), The University of Queensland, Australia Q4072

Address all correspondence and requests for reprints to: Robin Mortimer, Department of Endocrinology, Royal Brisbane Hospital, Herston, Q4029, Australia.

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 µg/mL and 40 µg/mL) and MMI (1.5 µg/mL and 15 µg/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.

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