The effect of lipophilicity on the hepatobiliary properties of iminodiacetic acid derivatives in the conditions of hyperbilirubinemia
Jovanovic, M. S.
Marković, Bojan D.
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The partition coefficients (log P) of theoretically possible alkyliodinated iminodiacetic acid (IDA) derivatives and commercial IDA derivatives were calculated using two computer programs: ChemSketch Log P and ChemOffice Ultra. Newly synthesized ligands (DIETHYLIODIDA and DIISOPROPYLIODIDA) with the highest calculated log P were labeled with technetium-99m. The biodistribution and the influence of bilirubin on their biokinetics were investigated in rats and compared to corresponding results for commercial Tc-99m-BROMIDA. Log P of Tc-99m-complexes of synthesized ligands were determined experimentally as well as the protein binding. In comparison to Tc-99m-BROMIDA, Tc-99m-DIETHYLIODIDA has: (a) better biliary excretion (2.76 +/- 0.15%ID/g versus 1.83 +/- 0.10%ID/g); (b) faster hepatic clearance (2.90 +/- 0.21%ID/g versus 7.47 +/- 0.70%ID/g) and decreased biliary excretion (for 14% versus 22%) in conditions of hyperbilirubinemia after 15 min. It is proved that Tc-99m-DIISOPROPYLIODIDA has... a prolonged hepatic transit time and decreased biliary excretion. (c) 2012 Elsevier Ltd. All rights reserved.