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Changes in plasma drug binding and alpha 1-acid glycoprotein in mother and newborn infant
Insights
Drug binding to alpha 1-acid glycoprotein differs in mothers and newborns due to varying protein levels. Factors like pregnancy and oral contraceptives also impact drug binding, affecting drug efficacy and safety.
Area of Science:
- Pharmacology
- Clinical Chemistry
- Neonatal Medicine
Background:
- Many drugs bind to alpha 1-acid glycoprotein (AAG) in plasma.
- Age-related changes in AAG can influence drug binding.
- Sex, pregnancy, and oral contraceptive use may affect drug-protein interactions.
Purpose of the Study:
- To investigate age-related changes in AAG and their influence on drug binding in mothers and newborns.
- To examine the effects of sex, pregnancy, and oral contraceptives on drug binding.
Main Methods:
- Equilibrium dialysis was used to determine drug binding.
- Drug binding was assessed in men, nonpregnant women, women using oral contraceptives, and mothers with their newborns.
- Plasma AAG concentrations were measured.
Main Results:
- The free fraction of several drugs (d-tubocurarine, metocurine, propranolol, lidocaine) was higher in neonates than in mothers.
- The free fraction of diazepam was lower in neonates than in mothers but higher than in nonpregnant women.
- Pregnant women showed higher free fractions for diazepam, propranolol, and lidocaine compared to nonpregnant women.
- Nonpregnant women using oral contraceptives had higher free fractions for diazepam and lidocaine than non-users.
- Fetal AAG levels were significantly lower than maternal AAG levels.
- Positive correlations were observed between AAG concentrations and the binding ratios of lidocaine and propranolol.
Conclusions:
- Lower AAG levels in fetuses contribute to the elevated free fraction of certain drugs.
- Pregnancy and oral contraceptive use alter drug binding patterns.
- These findings highlight the importance of considering AAG levels and physiological states in drug therapy, particularly in maternal and neonatal populations.
Abstract:
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.