METHIMAZOLE AND PROPYLTHIOURACIL EQUALLY CROSS THE PERFUSED HUMAN TERM PLACENTAL LOBULE

Propylthiouracil (PTU) is widely believed to cross the placenta less f reely than methimazole (MMI) and is therefore regarded as the preferre d 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 mu g/mL and 40 mu g/mL) and MMI(1.5 m u g/mL and 15 mu g/mL) in protein-free perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin. Both drugs readily c rossed the placenta, reaching equilibrium in all experiments in about 2 h. Drug concentrations in the two circuits fitted a two compartmenta l model. Transfer kinetics for the two drugs were similar, nonsaturabl e, 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 experi ments). There was no significant difference between drugs or drug dose s and no effect of addition of albumin. We conclude that PTU and MMI h ave similar placental transfer kinetics.