Analytical studies on beta-lactam antibiotics. II. Displacement effect of beta-lactam antibiotics on bilirubin bound to human serum albumin.
We established a method for determining the KD value as a measure of the bilirubin-displacing effect for drugs by using bilirubin oxidase, which is produced by Myrothecium verrucaria MT-1. This method makes it possible to conduct measurements of many beta-lactam antibiotics, including those which could not be determined by Brodersen's method. The KD values of latamoxef reported by many investigators based on Brodersen's method were higher than the true value owing to interaction of the drug with peroxidase and H2O2. Our KD value under the new enzyme conditions was 2.6 X 10(3). Little or no interaction of drug with the enzyme system was tentatively confirmed. Flomoxef, a newly developed drug, and 7432-S, under development in our company, had KD values of 0.4 X 10(3) and 2.8 X 10(3), respectively.
Matsuura
A
A
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Nagayama
T
T
Kitagawa
T
T
D000900:Anti-Bacterial Agents / Q000097:blood*; D001667:Binding, Competitive; D006863:Hydrogen-Ion Concentration; D003904:Mitosporic Fungi / Q000201:enzymology / Q000302:isolation & purification; D010088:Oxidoreductases / Q000097:blood*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013053:Spectrophotometry; D014462:Ultrafiltration; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D012709:Serum Albumin; D047090:beta-Lactams; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C042401:bilirubin oxidase