Endocrine Abstracts

JOINT149

Background: A very conceptual and uncomprehensive point in the strategy is that chelation of Bilirubin is not as easy as conjugation. It is bound to albumin within the circulation and soluble in fat. Besides, in contrast to general notion the lipophilic site of the molecule is not where conjugation occurs. Conjugation does not cover the fat-soluble side of the molecule but makes the molecule larger and more ware soluble from the water soluble pole. So, it is difficult to approach the molecule with solubilizing agents from the fat-soluble site because chelating agents are themselves water soluble. The only hope would be extraction of Bilirubin from albumin in the circulation and increasing the binding potential of albumin to extract bilirubin from fat rich tissues like the brain.

Aim: Increasing the “Albumin pool” to extract more unconjugated Bilirubin from fat rich tissues and hence therapeutic and prophylactic reduction of unconjugated bilirubin.

Methods: Twelve neonates with harmless hyperbilirubinemia in the range of 8mg/dl were treated with a single dose 500mg of a triguanide derivative called TR-225. Bilirubin was measured every half hour for 24 hours. Patients with stable levels under 2 were discharged from the hospital.

Results: TR-225 is 100% capable of reducing hyperbilirubinemia in all patients studied. The conjugate could be traced within the urine in a proportional manner. Speed of bilirubin reduction is 18 times that of exchange transfusion. The time/concentration curve denotes extreme effectiveness without rebound due to re-distribution of bilirubin from peripheral fat to circulation. The treatment is not without side effects and can hardly be used as a prophylaxis.

Conclusion: Treatment of neonatal hyperbilirubinemia with a chelator is chemically extremely difficult and needs sophisticated drug development techniques such as artificial intelligence. But it is a very interesting issue which can possibly close thousands of neonatal wards worldwide.