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Changes in plasma drug binding and α 1 ‐acid glycoprotein in mother and newborn infant
Author(s) -
Wood Margaret,
Wood Alastair J J
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.73
Subject(s) - free fraction , medicine , diazepam , lidocaine , propranolol , pregnancy , fetus , endocrinology , drug , phenytoin , pharmacology , pharmacokinetics , anesthesia , epilepsy , biology , genetics , psychiatry
A number of drugs bind to α 1 ‐acid glycoprotein in plasma. To determine whether age‐related changes in α 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 < 0.05), metocurine (p < 0.01), propranolol (p < 0.001), and lidocaine (p < 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 < 0.02), but higher than that in nonpregnant women (p < 0.001). The free fractions of diazepam, propranolol, and lidocaine were higher (p < 0.001) in pregnant women compared with nonpregnant women while the diazepam and lidocaine free fractions were higher (p < 0.05) in nonpregnant women on oral contraceptives than in women not using them. arAcid glycoprotein was lower in the fetus (15.3 ± 4.7 mg/100 ml) than the mother (49.6 ± 6.5 mg/100 ml) (p < 0.002). There was a positive correlation between plasma α 1 ‐acid glycoprotein concentrations and the binding ratio (bound/free concentrations) of lidocaine (p < 0.001; r = 0.623) and propranolol (p < 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 α 1 ‐acid glycoprotein. Clinical Pharmacology and Therapeutics (1981) 29, 522–526; doi: 10.1038/clpt.1981.73