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Clin Pharmacol Ther. 1981 Apr;29(4):522-6.

Changes in plasma drug binding and alpha 1-acid glycoprotein in mother and newborn infant.


A number of drugs bind to alpha 1-acid glycoprotein in plasma. To determine whether age-related changes in alpha 1-acid glycoprotein influence drug binding in mother and newborn infant and also the effects of sex, pregnancy, and oral contraceptives on drug binding, the binding of lidocaine, diazepam, propranolol, d-tubocurarine, and metocurine was determined by equilibrium dialysis in 17 men, 16 nonpregnant women, 16 nonpregnant women on oral contraceptives, and 15 mothers and their newborn infants at delivery. The free fraction of d-tubocurarine (p less than 0.05), metocurine (p less than 0.01), propranolol (p less than 0.001), and lidocaine (p less than 0.02) was higher in neonatal blood than in maternal blood, whereas the free fraction of diazepam was less in fetal cord blood than the mother's (p less than 0.02), but higher than that in nonpregnant women (p less than 0.001). The free fractions of diazepam, propranolol, and lidocaine were higher (p less than 0.001) in pregnant women compared with nonpregnant women while the diazepam and lidocaine free fractions were higher (p less than 0.05) in nonpregnant women and oral contraceptives than in women not using them. Alpha 1-acid glycoprotein was lower in the fetus (15.3 +/- 4.7 mg/100 ml) than the mother (49.6 +/- 6.5 mg/100 ml) (p less than 0.002). There was a positive correlation between plasma alpha 1-acid glycoprotein concentrations and the binding ratio (bound/free concentrations) of lidocaine (p less than 0.001; r = 0.623) and propranolol (p less than 0.001); r = 0.652), indicating that it is likely that the elevation of the free fraction of these drugs in the fetus is due in part to lower levels of alpha 1-acid glycoprotein.

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