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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 the protein binding rate of mesalazine pegylated prodrugs in different species of plasma, and investigate the effect of PEGylation on the drug protein binding rate. Methods: The content of drug in dialysis internal and external fluids was determined by plasma equilibrium dialysis method. The protein binding rate of drug and mouse plasma, dog plasma, rabbit plasma and bovine plasma were calculated. Results: The plasma protein binding rates of the mesalazine PEG compounds were (22.31 ± 5.28)%, (17.15 ± 3.21), respectively, lower, middle and high (1.08,1.35,1.62 mg · mL-1) %, (16.11 ± 4.55)%, respectively. The plasma of the dogs was (25.16 ± 5.87)%, (22.47 ± 4.14)% and (23.14 ± 3.46)%, (15.93 ± 2.31)% respectively; bovine plasma was (14.41 ± 6.21)%, (18.84 ± 7.80)% and (14.18 ± 5.23)% respectively. Conclusion: Mesalazine PEG has a low degree of plasma protein binding, with some differences among species. Compared with the prototype drugs, the drug PEGylation, plasma protein binding decreased.