Interindividual differences in the effect of drugs on bilirubin plasma binding in newborn infants and in adults

Abstract

The nonprotein-bound fraction of bilirubin was determined in undiluted plasma or serum from healthy adult volunteers and newborn infants after addition of unconjugated bilirubin, 12 mg/100 ml. There were significant interindividual difference (2-fold in 13 adults, 2.6-fold in 9 full-term newborn infants) in the free fraction value. Sulfisoxazole, salicylic acid, and salicyluric acid had a pronounced displacing effect on bilirubin in the 10 to 30 mg/100 ml drug concentration range. Aspirin had only a small effect at concentrations below 20 mg/100 ml. There was a very strong correlation between the free fraction value of bilirubin in individual samples of drug-free plasma and in the same plasmas after addition of any one of the 4 drugs studied. This shows that the relative increase of the free fraction of bilirubin induced by any one of the drugs was essentially the same but that the absolute increase varied greatly between subjects. It may be possible, therefore, to predict quanitatively the bilirubin-displacing effect of drugs in individual patients before drug administration by determining the free fraction of bilirubin in a plasma or serum sample obtained prior to initiation of drug therapy.