Plasma protein binding of bupivacaine in pregnant women at term.
The increased toxicity of bupivacaine in parturients is a well-known phenomenon. The reduced plasma protein binding of bupivacaine is one of the possible reasons. Therefore, we measured the free fraction of bupivacaine in plasma samples of parturients and non-pregnant volunteers. The free fraction was significantly higher in parturients (8.2% vs 5.4%) associated with a lower concentration of the alpha-1-acid glycoprotein (0.42 vs 1.01 g/l) and a higher concentration of progesterone (156 vs 0.4 ng/ml). The addition of progesterone to plasma samples of non-pregnant volunteers did not influence the free fraction of bupivacaine, whereas the addition of alpha-1-acid glycoprotein to the plasma of parturients decreased the free fraction significantly. Therefore, the lower concentration of this protein is the principal reason for the higher free fraction of bupivacaine in pregnancy and possibly one of the causes of the higher incidence of toxic side effects of bupivacaine in obstetric use.
Wulf
H
H
Department of Anaesthesiology, Hospital of Christian Albrechts University, Kiel, Federal Republic of Germany.
Münstedt
P
P
Maier
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001667:Binding, Competitive; D002045:Bupivacaine / Q000097:blood*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism*; D011247:Pregnancy / Q000097:blood*; D011374:Progesterone / Q000097:blood; D011485:Protein Binding
D009961:Orosomucoid; D011374:Progesterone; D002045:Bupivacaine