羧甲基壳聚糖/聚乙烯醇甲硝唑水凝胶片在Beagle犬体内的药动学

Pharmacokinetic study on CMCS/PVA-MTZ hydrogels in Beagle dogs

目的:考察羧甲基壳聚糖(CMCS)的取代度(DS)对羧甲基壳聚糖/聚乙烯醇(PVA)甲硝唑(MTZ)水凝胶片在Beagle犬体内缓释作用的影响。方法:以3种不同DS(0.43,0.57,0.69)的CMCS/PVA-MTZ水凝胶片为受试药品,以同剂量的MTZ普通片为参比药品,Beagle犬口服给药后在预定的时间点采血,用HPLC法测定血浆中的MTZ的浓度,计算其药动学参数,并进行比较。结果:主要药动学参数tmax、Cmax、Ka、AUC经方差分析及双单侧t检验后,3种CMCS/PVA-MTZ水凝胶片较普通MTZ片的各参数差异均有显著性(P<0.05),不同DS的CMCS/PVA-MTZ水凝胶片之间各个参数的差异有显著性(P<0.05),随着DS的降低,缓释作用愈加明显。结论:3种CMCS/PVA-MTZ水凝胶片较普通MTZ片在Beagle犬体内均有明显的缓释作用,而且其作用大小与CMCS的DS密切相关。

OBJECTIVE To study the pharmacokinetics of CMCS/PVA-MTZ hydrogels in Beagle dogs in order to estimate the effect of the substitutions of CMCS on the MTZ in vivo release from CMCS/ PVA hydrogels. METHODS Beagle dogs were orally treated with three different CMCS/PVA-MTZ hydrogels with various substitutions of CMCS and the common MTZ tablets at single dose,respectively. Plasma concentrations of MTZ were determined using HPLC. Pharmacokinetic parameters were calculated to study the influence of the substitution of CMCS on the MTZ sustained release from hydrogels. RESULTS The main pharmacokinetic parameters of tmax 、Cmax、Ka and AUC were tested by t-test. Significant differences were found in the pharmacokinetic parameters of three kinds of CMCS/PVA MTZ hydrogels compared to the common MTZ tablets （P〈0. 05）. And among the three different CMCS/PVA-MTZ hydrogels, there were significant differences when compared to one another （P〈0. 05）. With the decrease of substitute of CMCS, sustained release effect of MTZ was more significant. CONCLUSION The results indicate that the hydrogels all show sustained release in Beagle dogs and the effect is closely related with the substitute of CMCS.