title: Ceftriaxone--bilirubin-albumin interactions in the neonate: an in vivo study.
abstract: The in vivo bilirubin-albumin binding interaction of ceftriaxone (CRO) was investigated in 14 non-jaundiced newborns, aged 33-42 weeks of gestation, during the first few days of life after they had reached stable clinical condition. CRO (50 mg/kg) was infused intravenously over 30 min. The competitive binding effect of CRO on the bilirubin-albumin complex was estimated by determining the reserve albumin concentration (RAC) at baseline, at the end of CRO infusion, and at 15 and 60 min thereafter. Immediately after the end of drug administration, RAC decreased from 91.9 (+/- 25.1) mumol/l to 38.6 (+/- 10.1) mumol/l (P = 0.0001). At the same time the plasma bilirubin toxicity index (PBTI) increased from 0.64 (+/- 0.40) before drug infusion to 0.96 (+/- 0.44) thereafter (P = 0.0001). The highest displacement factor (DF) was calculated to be 2.8 (+/- 0.6) at the end of drug infusion. Average total serum bilirubin concentrations decreased from a baseline value of 59.6 (+/- 27.0) mumol/l to 55.2 (+/- 27.1) mumol/l (P = 0.026). Sixty minutes after the end of CRO infusion, RAC was 58.3 (+/- 21.7) mumol/l, PBTI regained baseline, but DF was still 1.9 (+/- 0.2). No adverse events were recorded. Our results demonstrate significant competitive interaction of CRO with bilirubin-albumin binding in vivo. Thus, ceftriaxone should not be given to the neonate at risk of developing bilirubin encephalopathy.
authors.affiliation: Department of Paediatrics, University Children's Hospital, Zürich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Fanconi
authors.forename: P
authors.initials: P
authors.lastname: Kälin
authors.forename: C
authors.initials: C
authors.lastname: Zwingelstein
authors.forename: C
authors.initials: C
authors.lastname: Crevoisier
authors.forename: W
authors.initials: W
authors.lastname: Ruch
authors.forename: R
authors.initials: R
authors.lastname: Brodersen
mesh_terms: D001663:Bilirubin / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D002443:Ceftriaxone / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D012709:Serum Albumin; D002443:Ceftriaxone; D001663:Bilirubin