Matsuura A, Nagayama T, Kitagawa T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Chemotherapy. 1988;34(4):345-53. doi: 10.1159/000238590.
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.
我们建立了一种使用疣孢漆斑菌MT-1产生的胆红素氧化酶来测定KD值的方法，以此作为衡量药物胆红素置换效果的指标。该方法能够对多种β-内酰胺抗生素进行测定，包括那些无法用布罗格森方法测定的抗生素。许多研究者基于布罗格森方法报告的拉氧头孢的KD值由于药物与过氧化物酶和过氧化氢的相互作用而高于真实值。在新的酶条件下我们测得的KD值为2.6×10³。初步确认药物与酶系统几乎没有相互作用。新开发的药物氟氧头孢以及本公司正在研发的7432-S的KD值分别为0.4×10³和2.8×10³。
