The effect of lipophilicity on the hepatobiliary properties of iminodiacetic acid derivatives in the conditions of hyperbilirubinemia.
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 (99m)Tc-BROMIDA. Log P of (99m)Tc-complexes of synthesized ligands were determined experimentally as well as the protein binding. In comparison to (99m)Tc-BROMIDA, (99m)Tc-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 15min. It is proved that (99m)Tc-DIISOPROPYLIODIDA has a prolonged hepatic transit time and decreased biliary excretion.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, Serbia.
J
J
Brborić
M S
MS
Jovanović
S
S
Vranješ-Đurić
O
O
Cudina
B
B
Marković
S
S
Vladimirov
D000814:Aniline Compounds; D000818:Animals; D001659:Biliary Tract / Q000000981:diagnostic imaging; D005998:Glycine; D006932:Hyperbilirubinemia / Q000000981:diagnostic imaging*; D007098:Imino Acids / Q000737:chemistry; D008099:Liver / Q000000981:diagnostic imaging; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012984:Software; D019784:Technetium Tc 99m Diethyl-iminodiacetic Acid / Q000737:chemistry; D019785:Technetium Tc 99m Disofenin / Q000737:chemistry
D000814:Aniline Compounds; D007098:Imino Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D019784:Technetium Tc 99m Diethyl-iminodiacetic Acid; C034837:technetium Tc 99m mebrofenin; D019785:Technetium Tc 99m Disofenin; D005998:Glycine; C008109:iminodiacetic acid