Drug binding in sera deficient in lipoproteins, albumin or orosomucoid

The relative role of lipoproteins, albumin and orosomucoid in the serum binding variation of various drugs was examined by separate removal of these proteins. Lipoproteins were removed from serum by ultracentrifugation, albumin by affinity chromatography and orosomucoid by immunoprecipitation. Removal of the lipoproteins did not affect the serum binding of the acidic (phenytoin) and neutral (digitoxin) drugs tested, nor the basic drugs disopyramide, quinidine or propranolol. A reduction in binding of amitryptyline, nortriptyline, doxepin and desmethyldoxepin was observed. Removal of albumin did, with some exception for nortriptyline, not affect the serum binding of the basic drugs tested. A pronounced reduction in the binding of phenytoin and digitoxin was observed. Removal of orosomucoid did not affect the binding of the acidic and neutral drugs tested. A reduction in the binding of all the basic drugs tested was observed, especially for disopyramide whose binding almost disappeared. Quinidine, propranolol, phenytoin and digitoxin all bound to isolated lipoproteins, but the removal of lipoproteins had no effect on the total serum binding for these drugs. Hence, the use of deficient sera provides valuable information as to the quantitative role of the various proteins in drug binding, whereas studies using purified proteins are often necessary to examine the mechanisms of the drug protein interactions.