中文摘要：

两性喹诺酮抗菌药通常含有一个羧基和一个氨基，这两个基团是产生抗菌活性所不可缺少的药效基团，同时也赋予了喹诺酮化合物在生理环境下独特的分子荷电性质．我们已测定了格帕沙星和HSR-903（olamufloxacin）的质子解离平衡常数，发现其等电点接近生理pH值（7．4）．由于其羧基和氨基在生理环境下均发生质子解离平衡，使得微小pH值变化导致分子荷电性质的突变，这种生理环境下pH值微小波动可通过静电作用力显著影响药物的体内过程，如与细胞内成分或受体的结合等．此外，我们的研究还表明格帕沙星和HSR-903高度分布到肺泡巨噬细胞内，其胞内与血浆药物浓度的比值超过100倍，蓄积机制可能是肺泡巨噬细胞胞浆内pH相对偏酸性以及与巨噬细胞膜内侧富含负电性磷脂酰丝氨酸的结合，从而导致其显著蓄积．

英文摘要：

In this paper the effect of the unusual molecular charge property of amphoteric quinolones, including grepafloxacin and olamufloxacin, on the binding to the negatively charged lipid membrane under the physiological conditions was investigated. The subtle pH variation around 7.4 can significantly change the molecular charge property of the two amphoteric quinolones, which results in a significant change of the electrostatic forces. The liposome/water system was undertaken to measure the drug-phospholipid membrane interactions. In the liquid-crystal liposome, the binding to membrane of the two quinolones was increased in the negatively charged liposome while decreased in the neutral liposome, with pH from 7.4 to 6. 8. Similarly, the same tendency occurred in the gel-state liposome, that the binding to membrane increased in the negatively charged liposome from 7.4 to 6. 8, mimicking drug transfer process from extracellular into intracellular fluid. In conclusion, the molecular electrical charge for amphoteric quinolones was very sensitive to pH variation around physiological pH, which may play an important role in the in vivo drug pharmacokinetics.