[N-乙酰-L-谷氨酸泼尼松龙前药的肾脏靶向特性]

[Kidney-targeting characteristics of N-acetyl-L-glutamic prednisolone prodrug].

作者信息

Su Min, He Qin, Zhang Zhi-rong, Hu Bin, Liu Shi-wei

机构信息

West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

出版信息

Yao Xue Xue Bao. 2003 Aug;38(8):627-30.

PMID:14628458

Abstract

AIM

To study the in vivo distribution of N-acetyl-L-glutamic prednisolone (ACEP) and to investigate the renal targeting characteristics of the prodrug.

METHODS

The concentrations of prednisolone in organs at predetermined time were assayed by HPLC after intravenous administration of ACEP or prednisolone to Kunming mice. The adverse effects were evaluated by testing the bone mineral densities (BMD) of Wistar rats.

RESULTS

The concentrations of prednisolone in kidney 15 min after i.v. administration were (86 +/- 8) microgram.g-1 for ACEP group, (57 +/- 4) microgram.g-1 for prednisolone group; 60 min after i.v. administration were (67 +/- 5) microgram.g-1 for ACEP group, (42 +/- 4) microgram.g-1 for prednisolone group. BMDs were (0.08 +/- 0.03) g.cm-2 and (0.14 +/- 0.06) g.cm-2 for prednisolone and ACEP-treated Wistar rats respectively.

CONCLUSION

Compared with the parent drug prednisolone, ACEP has kidney-targeting behavior and lower toxicity (n = 5, P < 0.001).

摘要

目的

研究N-乙酰-L-谷氨酸泼尼松龙（ACEP）的体内分布情况，并考察该前体药物的肾靶向特性。

方法

将ACEP或泼尼松龙静脉注射给昆明小鼠后，采用高效液相色谱法（HPLC）在预定时间测定各器官中泼尼松龙的浓度。通过检测Wistar大鼠的骨密度（BMD）来评估不良反应。

结果

静脉注射后15分钟，ACEP组肾脏中泼尼松龙的浓度为（86±8）微克·克⁻¹，泼尼松龙组为（57±4）微克·克⁻¹；静脉注射后60分钟，ACEP组为（67±5）微克·克⁻¹，泼尼松龙组为（42±4）微克·克⁻¹。泼尼松龙处理组和ACEP处理组Wistar大鼠的骨密度分别为（0.08±0.03）克·厘米⁻²和（0.14±0.06）克·厘米⁻²。