No abstract

The protein binding of furosemide was studied in the serum from 8 umbilical cords, in 51 children (aged between 2 weeks and 13.5 years) and in the plasma of 10 volunteers (aged between 28 and 42 years). The drug was added to the buffer to give a final concentration of 2 pg/ml. The unbound fraction of furosemide was 2.5 ± 0.1 % (cord serum) and 1.7 ± 0.7% (adult plasma). These figures are different at a level of 0.001. The unbound fraction of furosemide reached the adult values during the 1st year of life. A correlation (level of significance >0.01) was found between the unbound fraction and the age during the first 6 months of life. The furosemide binding kinetics were studied in 3 cord serum and in 3 adult plasma samples. The concentration of the drug in the buffer ranged between 1 and 16 pg/ml. The kinetic constants (mean ± SEM) were: association constant (K = 10^5 M^-) 2.4 ± 0.3 (cord serum), 2.0 ± 0.2 (adult plasma); the number of binding sites per gram protein (n = 10^-6) was 3.2 ± 0.5 (cord serum) and 3.9 ± 0.7 (adult plasma). When the concentration of furosemide was increased up to 200 pg/ml buffer, the free fraction of the drug increased up to 4.8 ± 0.2% (cord serum) and 2.9 ± 0.4% (adult plasma).

Clonazepam protein binding was investigated in sera from five different umbilical cords, 45 children (aged 2 mo to 12 yr), and five adults (aged 27 to 40 yr). The unbound fraction (means +/- SE) of clonazepam was 17.3% +/- 0.7% in umbilical cord serum and 13.9% +/- 0.2% in adult serum (P less than 0.01). In children, the unbound fraction of clonazepam reached the adult values during the first year of life. The kinetics of clonazepam serum protein binding were studied in three umbilical cord serum and three adult serum specimens. The number of binding sites (n, reported as moles per gram protein) and the association constant (K, reported as M-1) were estimated from double reciprocal plots of 1/r against 1/D (r is the number of moles bound per gram plasma protein; D is the molar concentration of unbound drug). In umbilical cord sera, the mean values (+/- SE) of n and K were 8.4 +/- 0.6 X 10(-7) mol/gm and 8.3 +/- 0.9 X 10(4) M-1. In adult serum samples the corresponding values were 3.0 +/- 0.8 X 10(-7) mol/gm and 2.7 +/- 0.6 X 10(5) M-1, which indicated lower binding capacity but higher affinity for clonazepam of plasma proteins in adults than in children.