Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide
Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide
复制标题
DOI：
10.1128/aac.37.10.2173
复制
发表时间：
1993-10
影响因子：
4.9
通讯作者：
M. Tanaka;T. Kurata;C. Fujisawa;Y. Ohshima;H. Aoki;O. Okazaki;H. Hakusui
中科院分区：
文献类型：
--
作者：
M. Tanaka;T. Kurata;C. Fujisawa;Y. Ohshima;H. Aoki;O. Okazaki;H. Hakusui
本文研究了氢氧化铝与左氧氟沙星合用时吸收减少的机理。LVFX（0.1 mM）在氯仿和磷酸盐缓冲液（pH 5.0）之间的分配系数随着金属离子如Cu 2+、Al 3+和Fe 2+（0.8 mM）的加入而降低60 - 70%，这表明形成了LVFX-金属离子螯合物。然而，在原位再循环实验中，合成的LVFX-Al 3+（1：1）螯合物（6.75 mM）和LVFX（6.75 mM）之间在大鼠肠道的吸收没有显著差异。另一方面，Al（NO3）3（1.5 mM）在原位连接环实验中显著抑制LVFX（1.5 mM）的吸收，抑制率为对照的20%，其中在给药溶液中观察到氢氧化铝的部分沉淀。氢氧化铝对LVFX和OFLX的吸附符合Langmuir方程，吸附容量分别为7.0 mg/g和7.4 mg/g，K值分别为1.77 × 10 ~（4）M ~（-1）和1.42 × 10 ~（4）M ~（-1）。氢氧化铝（2.5mg/ml）对5 0 μ M喹诺酮类药物的吸附率为诺氟沙星（NFLX）（72.0%）>依诺沙星（ENX）（61.0%）> OFLX（47.2%），约为LVFX（48.1%）。吸附喹诺酮类药物的洗脱率为LVFX（17.9%）> OFLX（20.9%）> ENX（18.3%）> NFLX（11.9%）。这些结果有力地表明，喹诺酮类药物的吸附氢氧化铝再沉淀在小肠将发挥重要作用，降低喹诺酮类药物的生物利用度后，与含铝抗酸剂共同管理。
The mechanisms of reduction in absorption of levofloxacin (LVFX) by coadministration of aluminum hydroxide were studied. The partition coefficient of LVFX (0.1 mM) between chloroform and phosphate buffer (pH 5.0) was reduced by 60 to 70% with the addition of metal ions such as Cu2+, Al3+, and Fe2+ (0.8 mM), which indicated the formation of LVFX-metal ion chelates. However, there was no significant difference in absorption from rat intestine between the synthetic LVFX-Al3+ (1:1) chelate (6.75 mM) and LVFX (6.75 mM) in an in situ recirculation experiment. On the other hand, Al(NO3)3 (1.5 mM) significantly inhibited the absorption of LVFX (1.5 mM) by 20% of the control in the in situ ligated loop experiment, in which partial precipitation of aluminum hydroxide was observed in the dosing solution. Data for adsorption of LVFX and ofloxacin (OFLX) from aqueous solution by aluminum hydroxide were shown to fit Langmuir plots, and the adsorptive capacities (rmax) and the K values were 7.0 mg/g and 1.77 x 10(4) M-1 for LVFX and 7.4 mg/g and 1.42 x 10(4) M-1 for OFLX, respectively. The rate of adsorption of several quinolones (50 microM) onto aluminum hydroxide (2.5 mg/ml) followed the order norfloxacin (NFLX) (72.0%) > enoxacin (ENX) (61.0%) > OFLX (47.2%) approximately LVFX (48.1%). The elution rate of adsorbed quinolones with water followed the rank order LVFX (17.9%) approximately OFLX (20.9%) approximately ENX (18.3%) > NFLX (11.9%). These results strongly suggest that adsorption of quinolones by aluminum hydroxide reprecipitated in the small intestine would play an important role in the reduced bioavailability of quinolones after coadministration with aluminum-containing antacids.