Shimada J, Hori S, Oguma T, Yoshikawa T, Yamamoto S, Nishikawa T, Yamada H
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
J Pharm Sci. 1993 May;82(5):461-5. doi: 10.1002/jps.2600820506.
Isomerization of ceftibuten to trans-ceftibuten, a less active isomer of ceftibuten, was observed in human serum in vitro. Investigation of the isomerization mechanism in the serum clarified that albumin accelerated the isomerization. The isomerization rate constant correlated significantly with the percent of binding to albumin, suggesting the binding of ceftibuten to albumin might be the driving force for the isomerization under in vitro conditions. This isomerization was also observed in clinical studies in humans. Results of physiological model analysis indicate that the isomerization catalyzed by albumin contributes significantly to the overall isomerization in the human body following oral administration.
在体外人血清中观察到头孢布烯异构化为反式头孢布烯，反式头孢布烯是头孢布烯活性较低的异构体。对血清中异构化机制的研究表明，白蛋白加速了异构化过程。异构化速率常数与头孢布烯与白蛋白的结合百分比显著相关，这表明在体外条件下，头孢布烯与白蛋白的结合可能是异构化的驱动力。在人体临床研究中也观察到了这种异构化现象。生理模型分析结果表明，口服给药后，白蛋白催化的异构化对人体内的整体异构化有显著贡献。
