Experimental studies and evaluation on safety of compound aluminum sulfate injection

Abstract

Abstract: AIM: To study the in situ stimulation ef-fect of compound aluminum sulfate injection after i.m. in rabbit quadriceps and dog bladder.The absorption of aluminum and the healing of the bladder wall were also studied to give an evaluation on the safety of the com-pound injection.METHODS: Compound aluminum sul-fate injection was i.m.injected into quadriceps of the rabbits.The in situ stimulation effect was observed mac-rographically.Blood samples were collected at different time after i.m.injection.Aluminum concentrationswere determined by ICP-MS assay and simulated with DAS software.Tissue necrosis as well as the healing of the bladder wall were observed macrographically or pathologi-cally after the injection was given into dog bladder.RESULTS: Severe stimulation was observed after intra quad-riceps injection, however, there was no obvious elevation of blood aluminum concentration.The average AUC_0-24 was 2.93±1.82 mg·h·L^-1 (n =5), corresponding to a relative bioavailability of about 2.77%.Injecting in bladder muscle necrotized the bladder wall in situ, but fi-broblast generated and took place of the necrotized mem-brane and muscle four weeks after injection.There was no bleeding or perforation on the bladder wall.CONCLU-SION: Caused compound aluminum sulfate injection in situ necrosis which healed up in 4 weeks.Aluminum ab-sorption is very low after injection, giving a further expla-nation to the safety of the compound injection.

Key words: compound aluminum sulfate injection, bladder, stimulation effect, absorption

CLC Number:

R965.3

XU Feng-hua, FU Wei-jun, ZHANG Zhi-ping, WANG Xiao-xiong. Experimental studies and evaluation on safety of compound aluminum sulfate injection[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(5): 510-514.

References

1 Yang K, Ding Q.The treatment of bladder cancer[J].Foreign Medicine-Urinary System, 2000;20:228-9
2 Wang YM, Zhang SZ, Jing DS, Wu Y.Clinical analysis of 441 bladder cancer[J].J Practical Oncology, 2000;15:201-2
3 Xu FH, Zhang ZP, Gao XY, Guo DS.Experimental study on the effect andthe uptake of compoundaluminum sulfate injection after local administration[J].Chin Pharm J, 2001;36:542-4
4 Xiong LP, Chen SJ.Investigation of serum aluminum level of inpatientsin nanchang[J].Stud Trace Elements Health, 2003; 20:39-40, 43
5 Wu YH, Zhou ZM, Wang YL.Studies on effects of aluminum compounds on aluminum contentsinserum andbrain of mice with high performance capillary electrophoresis[J].China J Chin Mate Med, 2004;29:59-61
6 Lv WQ, Wang XM.Clinical study and trace aluminum test in 64 cases of chronic renal impairment[J].Stud Trace Elements Health, 2002;19:14-5
7 Wei XM, Lu JP, Wang QH, Mo LF, Huang YF, Huang B. Effects of aluminum electrolysis working environments on work-er' s nervous system function and trace element content[J]. Guangxi J Prev Med, 1999;5:257-60
8 Ou YL, Xu FH, Wang XY, Zhang ZP, Gao XY, Wang NF. Determination of trace aluminum in rabbit blood by ICP-MS[J]. Chin J Prev Med, 2002;36:46-7
9 Editorial committee, State Environmental Protection Administra-tion of China.Detectionmethods of water and waste water[M]. Beijing:China Environmental Science Publishing House, 1989: 70
10 ChenMS, Zhang YJ, Li JQ, Liang HH, Zhang YQ, Zheng Y. Randomized clinical trial of percutaneousradiofrequency ablation plus absolute ethanol injection compared with radiofrequency ab-lation alone for small hepatocellular carcinoma[J].Chin J On-cology, 2005;27:623-5
11 Ma MP, Ming JZ, Zhou YC, Hu DY.Local acetic acid injec-tion for treatment of experimental hepatic tumor[J].Radiol Practice, 2004;19:53-6
12 Qin QL, Ma XY, Chao GH, Li AQ, Liu HY, Chang J.Effect of local injection of Xiaozhiling on experimental gastric cancer [J].J Fourth Mil Med Univ, 2000;21:961-3
13 Fu WJ, Hong BF, Wang XX, LiuQ, Gao JP, Xu FH.Exper-imental study on the effects of compound aluminum sulfate injec-tion after bladder submucosal injection and its clinical signifi-cance[J].Chin J Exp Surg, 2004;21:79-80

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