Metabolism of propranolol in the human maternal-placental-foetal unit
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Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous maternal plasma levels for propranolol and its major metabolites (mean +/- SD) were: propranolol 0.32 +/- 0.17, propranolol glucuronide 0.86 +/- 0.36, 4-hydroxypropranolol 1.4 +/- 1.0, 4-hydroxypropranolol glucuronide 0.71 +/- 0.45 and naphthoxylactic acid 3.0 +/- 1.6. P binding in cord plasma at delivery was 67.2 +/- 3.9% (mean +/- SD) which was significantly less ('t' = 13.4, df = 13, p less than 0.001) than the P binding in maternal plasma at delivery (87.5 +/- 1.6%, mean +/- SD). The plasma protein binding (mean +/- SD) of naphthoxylactic acid in cord plasma (98.6 +/- 0.2%) was significantly greater ('t' = 3.808, df = 4, p less than 0.02) than the naphthoxylactic acid binding in maternal plasma at delivery (97.6 +/- 0.4%). When the simultaneous concentrations of P and naphthoxylactic acid in maternal and cord plasma are compared in conjunction with protein binding and ionic effects, it would seem that metabolism of P does occur in the placental/foetal unit.
Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous maternal plasma levels for propranolol and its major metabolites (mean +/- SD) were: propranolol 0.32 +/- 0.17, propranolol glucuronide 0.86 +/- 0.36, 4-hydroxypropranolol 1.4 +/- 1.0, 4-hydroxypropranolol glucuronide 0.71 +/- 0.45 and naphthoxylactic acid 3.0 +/- 1.6. P binding in cord plasma at delivery was 67.2 +/- 3.9% (mean +/- SD) which was significantly less ('t' = 13.4, df = 13, p less than 0.001) than the P binding in maternal plasma at delivery (87.5 +/- 1.6%, mean +/- SD). The plasma protein binding (mean +/- SD) of naphthoxylactic acid in cord plasma (98.6 +/- 0.2%) was significantly greater ('t' = 3.808, df = 4, p less than 0.02) than the naphthoxylactic acid binding in maternal plasma at delivery (97.6 +/- 0.4%). When the simultaneous concentrations of P and naphthoxylactic acid in maternal and cord plasma are compared in conjunction with protein binding and ionic effects, it would seem that metabolism of P does occur in the placental/foetal unit.