Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium

Abstract

The post-distributive neonatal:maternal plasma salicylate concentration ratio following salicylate administration to the mother before delivery is appreciably higher than unity. The protein binding of salicylate and the albumin concentration in one such plasma pair were considerably higher in the neonatal than in the maternal plasma. Equilibrium dialysis of neonatal plasma or serum from 6 newborn infants against that of their mothers produced a neonatal: maternal salicylate concentration ratio above unity in all cases even if the albumin concentration in the neonatal serum did not exceed that in the maternal serum. However, there was a strong correlation between the neonatal:maternal concentration ratios of salicylate and albumin. These observations demonstrate that conclusions concerning the distribution of a drug across the placenta in relation to its plasma protein binding characteristics must be based on the results of binding studies with plasma or serum from neonates and their mothers, and not from other adult subjects.

Investigations on salicylate protein binding in newborns and infants

“…The cord blood of the respective newborns showed a salicylate protein-binding which, when expressed as a percentage, was also reduced compared to the non-pregnant women but not to such an extent as in their mothers. Investigations carried out by the team of Levy [17] showed similar results: i.e. a reduction of salicylate proteinbinding in pregnant women, as well as a slightly less significant reduction of protein-binding in the newborn if the measurement was made on blood from the umbilical vein.…”

Low-Dose Aspirin in Pregnancy: Maternal and Neonatal Aspirin Concentrations and Neonatal Prostanoid Formation

“…12 The placental transfer of salicylic acid has been demonstrated in vivo. 39,40 After chronic ingestion of acetylsalicylic acid in antiinflammatory doses, plasma concentrations of salicylic acid are higher in the newborn infants than in the mothers because the protein binding of salicylic acid is considerably higher in neonatal than in maternal plasma. 39,40 Newborn infants mainly eliminate salicylic acid by conversion to the glycine and glucuronic acid conjugates.…”

“…39,40 After chronic ingestion of acetylsalicylic acid in antiinflammatory doses, plasma concentrations of salicylic acid are higher in the newborn infants than in the mothers because the protein binding of salicylic acid is considerably higher in neonatal than in maternal plasma. 39,40 Newborn infants mainly eliminate salicylic acid by conversion to the glycine and glucuronic acid conjugates. 40 The capacity of these pathways is very low, and elimination of salicylic acid by newborn infants is, therefore, much slower than in adults with a half-life of approximately 4 to 11 hours.…”

Mechanisms regulating toxicant disposition to the embryo during early pregnancy: An interspecies comparison

“…The distribution of salicylate in near-term human pregnancy favors the fetus, with neonatal:maternal salicylate concentration ratios of about 1.6 Levy et al, 1975). The concentration gradient of high concentrations in the fetus relative to the mother was attributed to greater protein binding in the term fetus, with comparable concentrations of free salicylate in the two compartments .…”

“…They assumed similar free valproic acid concentra- Garrettson et al (1975); Levy et al (1975) tions across the placenta at both gestation times (empirically confirmed at term by Nau et al, 1984) with protein bound valproic acid greater in the mother early in gestation and greater in the fetus in later gestation. The resulting model predicts total valproic acid concentrations of 60 and 10 mg/liter during early gestation in mother and fetus, respectively.…”