Disposition of the adrenergic blocker metoprolol and its metabolite OH-metoprolol in maternal plasma, amniotic fluid and capillary blood of the neonate.
Seven women were treated with metoprolol 50-100 mg twice daily for hypertension in pregnancy. The disposition of metoprolol and one of its metabolites alfa-OH-metoprolol was studied in venous plasma and amniotic fluid during labour, in mixed cord plasma and in capillary blood of the newborn. Peak concentrations of metoprolol and alfa-OH-metoprolol were reached 60 to 120 min after dosing in maternal plasma while the amniotic fluid levels of these compounds continued to increase from 60 to 180 min to the end of the study and were substantially higher than in the plasma after 4 to 5 h. It is postulated that a major fraction of metoprolol and alfa-OH-metoprolol reaches the amniotic fluid via the fetal urine and that the elimination from the amniotic fluid mainly proceeds via diffusion across fetal membranes and transfer across the fetal capillary bed. No measurable concentrations of metoprolol were found in two of the newborns 2 h after delivery. In the remaining four neonates the 2-h concentrations exceeded the corresponding cord plasma levels. In all neonates the alfa-OH-metoprolol levels in the capillary blood were higher 2 h after birth than in cord blood. In two newborns the metabolite levels continued to increase for 5 h and in one the highest blood concentrations of this metabolite was found 20 h after birth. Redistribution of metoprolol from tissue stores followed by metabolism might be the cause of these temporary elevations of the blood levels of metoprolol and alfa-OH-metoprolol.
Department of Obstetrics and Gynecology, Orebro Medical Center Hospital, Sweden.
S
S
Lindeberg
P
P
Lundborg
C G
CG
Regårdh
B
B
Sandström
D000653:Amniotic Fluid / Q000378:metabolism*; D002196:Capillaries; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy
D008790:Metoprolol