目的:测定美沙拉嗪PEG化前药在不同种属血浆中的蛋白结合率,考察PEG化对药物蛋白结合率的影响。方法:采用血浆平衡透析法,以紫外分光光度法对透析内液与外液中的药物含量进行测定,计算药物与小鼠血浆、犬血浆、兔血浆及牛血浆的蛋白结合率。结果:美沙拉嗪PEG化物的低、中、高(1.08,1.35,1.62 mg·mL^-1)3种质量浓度的小鼠血浆蛋白结合率分别为(22.31±5.28)%,(17.15±3.21)%,(16.11±4.55)%;犬血浆为(25.16±5.87)%,(22.47±4.14)%,(23.14±3.46)%;兔血浆为(17.13±8.26)%,(13.87±6.32)%,(15.93±2.31)%;牛血浆为(14.41±6.21)%,(18.84±7.80)%,(14.18±5.23)%。结论:美沙拉嗪PEG化物血浆蛋白结合程度较低,种属间存在一定差异。与原型药物相比,药物经PEG化后,血浆蛋白结合呈下降趋势。

OBJECTIVE To determine protein binding rates of mesalazine-PEG prodrug in plasma from different species, and to examine impacts of PEGylation on plasma protein binding rates.METHODS Equilibrium dialysis method was carried out to determine plasma protein binding rates in mouse plasma, dog plasma, rabbit plasma and bovine plasma. Ultraviolet spectrophotometry was employed to determine concentration of drugs inside or outsides of dialysis membrane, and then protein binding rate was calculated.RESULTS Plasma protein binding rates of mesalazine-PEG conjugates at low, middle and high concentrations in different species were as follows. Plasma protein binding rates were (22.31±5.28)%, (17.15±3.21)%, (16.11±4.55)% in mouse plasma, (25.16±5.87)%, (22.47±4.14)%, (23.14±3.46)% in dog plasma, (17.13±8.26)%, (13.87±6.32)%, (15.93±2.31)% in rabbit plasma, and (14.41±6.21)%, (18.84±7.80)%, (14.18±5.23)% in bovine plasma, respectively.CONCLUSION Plasma protein binding of mesalazine-PEG conjugates is at low strength and there are some differences between species. Compared with prototype drugs, plasma protein binding rates of mesalazine-PEG conjugates tend to decrease after PEGylation.