COVALENT BINDING OF A BUCILLAMINE DERIVATIVE WITH ALBUMIN IN SERA FROM HEALTHY-SUBJECTS AND PATIENTS WITH VARIOUS DISEASES

Purpose. To investigate the difference of pharmacokinetics of thiol-co ntaining drugs in various disease states, we studied the covalent bind ing of SA3786, a bucillamine derivative, with proteins in patient seru m compared with that in healthy serum. Methods. Sera from healthy volu nteers and patients of various diseases were supplied by the Japanese Red Cross Kumamoto Hospital. For the formation of conjugate experiment s, SA3786 was added to a final concentration of 7 x 10(-4) M. After 6h incubation at 37 degrees C, HPLC analysis of 5 mu l aliquots of each sample was performed using a column of N-methylpyridinium polymer (4VP -Me). Results. The extent of HSA-SA3786 conjugate formation was found to be lower in the sera from healthy volunteers (control) than those f rom patients of various diseases. Especially high reactivity with SA37 86 was observed in sera from rheumatic patients and hepatic patients. With the exception of the fraction of mercaptoalbumin (f(HMA)), none o f the parameters showed a good correlation with conjugate formation. C onclusions. The parameter f(HMA) must be considered to be one of the m ost important factors in formation of conjugates between plasma protei n and thiol compounds. However, other factors may be involved in addit ion to f(HMA) although the nature of these factors is not clear.