Placental transfer of beta-adrenergic antagonists studied in an in vitro perfusion system of human placental tissue

Abstract

Maternofetal transfer of five beta-blockers differing in molecular weight, solubility, and binding to albumin was studied using a dual in vitro perfusion system of an isolated cotyledon of human placenta. At steady state the diffusion rate of the lipid-soluble propranolol, timolol, and labetalol was three to four times higher than that of the hydrophilic atenolol and celiprolol. Albumin binding had no significant effect on diffusion when equal concentrations were used in the two perfusion circuits. With increased albumin concentration on the fetal side an acceleration of the diffusion of propranolol could be shown. Propranolol and labetalol showed considerable binding to placental tissue. After bolus injection transfer was clearly suppressed, as a result of tissue binding, and there was a delay until a steady state of diffusion was reached when constant concentrations were maintained in the maternal compartment. With recirculation of the fetal and maternal compartments propranolol rapidly equilibrated in the two perfusion circuits at 35% of the initial level in the maternal circuit. Atenolol after 4 hours of recirculation had not reached full equilibration between the two compartments, and the fetal concentration was at 55% of the initial level on the maternal side.