Bilirubin displaces furosemide from serum protein: the effect is greater in newborn infants than adult subjects.

The protein binding of furosemide was studied in the serum from 7 umbilical cords and 7 healthy adult subjects in presence or absence of bilirubin. In cord serum, the unbound fraction of furosemide (mean +/- SD) was 2.32 +/- 0.14 (control), 2.94 +/- 0.26 (200 microM bilirubin) (p less than 0.001) and 3.52 +/- 0.38 (400 microM bilirubin) (p less than 0.001). Percent increase (mean +/- SD) of the unbound furosemide was 22 +/- 11 and 51 +/- 12 after 200 and 400 microM bilirubin, respectively. In adult serum, the unbound fraction of furosemide was 1.69 +/- 0.21 (control), 1.93 +/- 0.24 (200 microM bilirubin) and 2.15 +/- 0.38 (400 microM bilirubin). Percent increase of the unbound fraction was 14 +/- 8 and 28 +/- 16 after 200 and 400 microM bilirubin, respectively. Binding of furosemide was also studied in 5 cord and adult serum specimens previously dialysed for 18 h at 4 degrees C. Unbound furosemide in dialyzed serum was 1.39 +/- 0.05 (cord) and 1.25 +/- 0.04 (adult). Cord serum contains dialyzable compounds that enhance the unbound fraction of furosemide. Displacement effect of bilirubin was unchanged by dialysis and it was significantly higher in cord than adult serum. The different displacing effect of bilirubin might suggest the presence of qualitatively different albumin in cord serum.