复方硫酸铝注射液新西兰兔静脉注射和局部注射药代动力学研究

目的研究复方硫酸铝注射液静脉注射后的药代动力学以及肌肉和皮下注射后的全身吸收.方法兔耳静脉、股四头肌和背部皮下注射,耳静脉采血,采用等离子体质谱法测定血铝浓度,DAS药代动力学程序处理血药浓度数据.结果静脉注射复方硫酸铝注射液1 mg·kg-1 (剂量均以无水硫酸铝计),硫酸铝体内药代动力学过程符合二房室模型,t1/2β为 1.08±0.46 h,AUC0-12h为 1.52±0.92 mg·h·L-1(n=5).股四头肌注射复方硫酸铝注射液80 mg·kg-1,血铝浓度略有升高,但不明显,采用梯形法计算曲线下面积,平均AUC0-24h为 2.93±1.82 mg·h·L-1(n=5),相对生物利用度约为 2.41%.皮下注射160 mg·kg-1,血铝浓度没有明显的峰值,平均AUC0-24h为 0.88±1.14 mg·h·L-1(n=5),相对生物利用度约为 0.36%.结论复方硫酸铝注射液静脉注射后血液中清除速率快,局部注射后全身吸收量很低,是一种安全的新制剂.

Pharmacokinetic study on compound aluminum sulfate injection after i.v. and in situ administration in rabbits

AIM: To study the pharmacokinetics of compound aluminum sulfate injection after i.v. administration and aluminum absorption after i.m. and s.c. administration in New Zealand rabbits. METHODS: Compound aluminum sulfate injection was administrated i.v. to the left-ear at the dose of 1 mg·kg-1, i.m. in quadriceps at the dose of 80 mg·kg-1 or s.c. under back skin at the dose of 160 mg·kg-1 (anhydrous aluminum sulfate/body weight). Blood samples were collected at different time after injection from the right-ear vein. ICP-MS assay was used to determine the aluminum (Al) concentration. Pharmacokinetic parameters were calculated with DAS program. RESULTS: The blood Al concentration-time profiles after i.v. injection fitted to a two-compartment model, with t1/2β 1.08±0.46 h and AUC0-12h 1.52±0.92 mg·h·L-1 (n=5). There was no obvious increase in Al concentration after i.m. injection of 80 mg·kg-1 or s.c. injection of 160 mg·kg-1 aluminum sulfate. The average AUC0-24h of i.m. injection was 2.93±1.82 mg·h·L-1(n=5), and that of s.c. injection was 0.88±1.14 mg·h·L-1(n=5), corresponding to the bioavailability of i.m. and s.c. injection being about 2.41% and 0.36%, respectively. CONCLUSION: Blood Al eliminates very quickly. The absorbed Al after i.m. or s.c. injection is very low, suggesting compound aluminum sulfate injection a safe preparation.