Biochemical characterization of x-ray contrast media.
OBJECTIVE
Eleven ionic and nonionic contrast media were compared in parallel regarding their effects on various biochemical parameters in vitro. Partition coefficient, protein binding, release of histamine, hemolysis inhibition and complement activation were determined as well as inhibition of various enzymes. Additionally, incompatibilities between contrast media and intravascular drugs that often are coadministered were determined.


METHODS
Partition coefficients were determined in the system n-butanol/water by spectrophotometry. Protein binding was measured by equilibrium dialysis. Histamine release from rat peritoneal mast cells was measured by radioassay. Hemolysis inhibition and complement activation was determined in beagle dog serum using antibody-coated sheep erythrocytes. The inhibition of enzyme systems was measured photometrically. Incompatibility with coadministered drugs was registered by appearance of precipitations.


RESULTS
Hydrophilicity as determined by partition coefficients was highest for iotrolan and lowest for iotetrol. Protein binding ranged from practically zero for most substances to 14% for ioxaglate. Histamine release was highest for diatrizoate (77% at 100 mg I/mL) and lowest for iodixanol (1%). Complement activation at 100 mg I/mL ranged from 0% (diatrizoate, iopamidol) to 77% (iopentol). The inhibition of the enzyme systems urokinase, streptokinase, collagenase, tissue plasminogen activator, and lysozyme was lowest for the nonionic dimers.


CONCLUSIONS
All compounds influenced the parameters tested. However, the degree of interaction was different. Although there was no significant correlation between hydrophilicity (partition coefficient) or osmolality and the tested parameters, nonionic dimers seemed to be superior to nonionic monomers. The reason might lie in reduced chemotoxicity of this class of contrast media.
Krause
W
W
Research Laboratories of Schering AG, Berlin, Germany.
Niehues
D
D
D020001:1-Butanol; D000818:Animals; D001669:Biochemical Phenomena; D001671:Biochemistry; D000440:Butanols / Q000737:chemistry; D011232:Chemical Precipitation; D003167:Complement Activation; D003287:Contrast Media / Q000737:chemistry* / Q000494:pharmacology; D003973:Diatrizoate / Q000737:chemistry; D004285:Dogs; D004344:Drug Incompatibility; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006461:Hemolysis; D006636:Histamine Release; D007458:Iodipamide / Q000031:analogs & derivatives / Q000737:chemistry; D007479:Iopamidol / Q000737:chemistry; D007485:Ioxaglic Acid / Q000737:chemistry; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009113:Muramidase / Q000037:antagonists & inhibitors; D010783:Photometry; D011485:Protein Binding; D051381:Rats; D012756:Sheep; D013053:Spectrophotometry; D013300:Streptokinase / Q000037:antagonists & inhibitors; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors; D014283:Triiodobenzoic Acids / Q000737:chemistry; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors; D014867:Water
D000440:Butanols; D003287:Contrast Media; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D014283:Triiodobenzoic Acids; C010202:iotetroxide; D014867:Water; D003973:Diatrizoate; C033300:iotrolan; C053571:iopentol; D020001:1-Butanol; D009113:Muramidase; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; C044834:iodixanol; D007479:Iopamidol; D007458:Iodipamide; D007485:Ioxaglic Acid