Binding of ¹⁴C-Salicylic Acid and ¹⁴C-PentobarbitaI to Plasma Proteins of Several Species During the Perinatal Period

Abstract

The fractional binding of ¹⁴C-salicylic acid and ¹⁴C-pentobarbital was studied as a function of age in plasma of the pig, dog, goat and human. The pig exhibited an unusual degree of hypoalbuminemia and low fractional binding of salicylic acid at birth. Albumin levels and the percent binding of salicylic acid were not significantly lower in newborn plasma than in adult plasma of the other species studied. The pig was also exceptional in that the high fractional binding of pentobarbital observed at low Iigand concentrations in plasma of the newborn was not observed in the other species studied. Depletion of albumin in newborn pig plasma did not appreciably affect the binding of pentobarbital. Thus it is suggested that the plasma of the fetal and newborn pig may contain a nonalbuminoid protein, such as a fetal globulin, which is capable of binding pentobarbital but does not have a high avidity for salicylic acid. It apparently does not exist at birth in the plasmas of the other species studied, as depletion of albumin markedly reduced the fractional binding of pentobarbital.

Enantioselective pharmacokinetics of ketoprofen in piglets: the significance of neonatal age

“…, 1974; Morselli et al. , 1980) and in addition, pigs exhibit a pronounced degree of hypoalbuminemia at birth (Short et al. , 1975; Egeli et al.…”

“…Nonsteroidal anti-inflammatory drugs display a high degree of plasma protein binding (Lees et al, 2004) and are mainly bound to albumin (Lapicque et al, 1993). The affinity of albumin for acidic drugs increases from birth into early infancy (Windorfer et al, 1974;Morselli et al, 1980) and in addition, pigs exhibit a pronounced degree of hypoalbuminemia at birth (Short et al, 1975;Egeli et al, 1998). Egeli et al (1998) found that the serum albumin concentration in 1-day-old piglets was 11 g ⁄ L and this had increased to 32 g ⁄ L by the time the piglets were 21 days old.…”

Clinical Pharmacokinetics in Neonates

“…Other compounds for which a decreased plasma protein binding has been observed in the newborn include: sulphaphenazole (Chignell et al, 197 1), sulphadimethoxine and sulphamethoxydiazine (Ganshorn and Kurz, 1968), sulphamelhoxypyrazine (Sereni et aI., 1968), benzy lpenicillin and ampicillin (Ehrnebo et aI., 1971), nafcillin (Krasner et aI., 1973), imipramine (Pruitt and Dayton, 1971), desmethylimipramine (Rane et aI., 1971) and pentobarbitone (Short et a\., 1975).…”