caa a22 4500 477126936 CHVBK 20180405111652.0 cr unu---uuuuu 170330e19970301xx s 000 0 eng 10.1023/A:1012006306915 doi (NATIONALLICENCE)springer-10.1023/A:1012006306915 Covalent Binding of a Bucillamine Derivative with Albumin in Sera from Healthy Subjects and Patients with Various Diseases [Elektronische Daten] [Ryuichi Narazaki, Masaki Otagiri] Purpose. To investigate the difference of pharmacokinetics of thiol-containing drugs in various disease states, we studied the covalent binding of SA3786, a bucillamine derivative, with proteins in patient serum compared with that in healthy serum. Methods. Sera from healthy volunteers and patients of various diseases were supplied by the Japanese Red Cross Kumamoto Hospital. For the formation of conjugate experiments, SA3786 was added to a final concentration of 7 × 10−4M. After 6h incubation at 37°C, HPLC analysis of 5 μ1 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 from patients of various diseases. Especially high reactivity with SA3786 was observed in sera from rheumatic patients and hepatic patients. With the exception of the fraction of mercaptoalbumin (fHMA), none of the parameters showed a good correlation with conjugate formation. Conclusions. The parameter fHMA must be considered to be one of the most important factors in formation of conjugates between plasma protein and thiol compounds. However, other factors may be involved in addition to fHMA although the nature of these factors is not clear. Plenum Publishing Corporation, 1997 covalent binding nationallicence serum albumin nationallicence bucillamine nationallicence mercapto ratio nationallicence Narazaki Ryuichi Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut Otagiri Masaki Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/3(1997-03-01), 351-353 0724-8741 14:3<351 1997 14 11095 https://doi.org/10.1023/A:1012006306915 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012006306915 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Narazaki Ryuichi Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut NATIONALLICENCE 700 1- Otagiri Masaki Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/3(1997-03-01), 351-353 0724-8741 14:3<351 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer