溴吡斯的明N-三甲基壳聚糖包衣脂质体兔体内药动学研究

Pharmacokinetics and relative bioavailability of pyridostigmine bromide-loaded liposomes with N-trimethyl chitosan coating in rabbits

目的考察N-三甲基壳聚糖(TMC60)包衣溴吡斯的明脂质体(PB-L)在兔体内的药动学特征。方法 9只新西兰大耳白兔随机分成3组,采用自身交叉对照实验,分别单剂量口服TMC60包衣PB-L、未包衣PB-L及市售PB普通片,采用HPLC法测定血浆中PB的浓度,用DAS2.1.1软件计算药动学参数,并计算包衣PB-L及未包衣PB-L相对于市售PB普通片的相对生物利用度。结果 TMC60包衣PB-L、未包衣PB-L及市售PB普通片在兔体内的药动学特征符合二室模型,主要药动学参数如下:Cmax分别为(15.131±0.244)mg·L-1,(15.430±0.512)mg·L-1和(17.596±0.484)mg·L-1;tmax分别为(4.52±0.24)h,(4.05±0.15)h和(2.33±0.28)h;AUC0-∞分别为(252.928±5.014)mg·h·L-1,(222.644±4.243)mg·h·L-1和(196.553±2.982)mg·h·L-1;TMC60包衣PB-L及未包衣PB-L的相对生物利用度分别为128.682%、101.573%,经方差分析、双单侧t检验和非参数检验,TMC60包衣PB-L比市售普通片生物利用度显著提高(P<0.05),未包衣PB-L与普通片比较差异无统计学意义(P>0.05)。结论 TMC60包衣PB-L可显著提高兔体内生物利用度。

Objective To study the pharmacokinetics and relative bioavailability of N-trimethyl chitosan（TMC60）-coated pyridostigmine bromide liposomes（PB-L） in rabbits.Methods Nine New Zealand rabbits were randomly divided into three groups.Based on the self-crossover control experiment,the rabbits were subjected to single-dose oral administration of TMC60-coated PB-L,uncoated PB-L and marketed PB tablets,respectively.The PB concentrations in the rabbit plasma were determined by HPLC,and the DAS 2.1.1 software was applied to calculate the pharmacokinetic parameters and relative bioavailability.Results The pharmacokinetic property of TMC60-coated PB-L,uncoated PB-L and marketed PB tablets were fitted with two-compartment model with the main pharmacokinetic parameters as follows： Cmax of（15.131±0.244）mg·L^-1,（15.430±0.512）mg·L^-1 and（17.596±0.484）mg·L^-1,tmax of（4.52±0.24）h,（4.05±0.15）h and（2.33±0.28）h,AUC0-∞ of（252.928±5.014） mg·h·L^-1,（222.644±4.243） mg·h·L^-1 and（196.553±2.982）mg·h·L^-1.The relative bioavailability of TMC60-coated PB-L and uncoated PB-L was 128.682% and 101.573%,respectively.Through variance analysis,two one sided t-test and nonparametric test,the bioavailability of TMC60-coated PB-L was increased significantly（P0.05） while that of uncoated PB-L showed no notable difference when compared with that of PB tablets（P0.05）.Conclusion TMC60-coated PB-L showed the increased bioavailbility in rabbit.