5-氨基水杨酸锌结肠定位肠溶胶囊在人体内的转运释放和吸收

Transport release and absorption of zinc 5-aminosalicylate colon targeting capsules in human

目的观察5-氨基水杨酸锌结肠定位肠溶胶囊的体内转运释放和吸收特征。方法健康受试者和轻、中度溃疡性结肠炎患者各10例,定时X线拍片观察胶囊在体内的位置和溶解情况;同时检测血浆5-氨基水杨酸(5-ASA)和乙酰-5-氨基水杨酸(AC-5-ASA)及锌离子浓度。结果 10例健康受试者:胶囊到达升结肠的平均时间为(5.80±1.99)h,胶囊崩解平均时间为(8.00±1.63)h。10例患者:胶囊到达升结肠的平均时间为(6.80±3.65)h,崩解的平均时间为(9.75±2.50)h。9例健康受试者:口服5-氨基水杨酸锌1.0 g,5-ASA主要参数Tmax为(12.33±1.73)h,Cmax为(325.72±197.52)μg.L-1,AUC0→t为(3.66±2.26)mg.L-1.h;排泄总量:5-ASA为(94.4842±61.3647)mg,AC-5-ASA为(120.4207±78.2098)mg,经尿液排泄的5-ASA约为剂量的9.4%。8例患者:口服5-氨基水杨酸锌1.0 g,5-ASA主要参数Tmax为(11.38±5.72)h,Cmax为(235.83±177.90)μg.L-1,AUC0→t为(3.19±1.58)mg.L-1.h。结论 5-氨基水杨酸锌结肠定位肠溶胶囊能在溃疡性结肠炎患者及健康受试者结肠定位释药,两者释放特征、吸收情况相近。

Objective To investigate the transport, release and absorption characteristics of zinc 5 - aminosalicylate colon targeting capsules in human. Methods A single oral dose of 1.0 g zinc 5 - aminosalicylate colon targeting capsules was administered to 10 healthy volunteers or 10 patients with mild or moderate ulcerative colitis. The position and dissolution of the capsules was observed with X - ray at different time points, and the concentration of 5 -aminosalicylic acid（5 -ASA） , acetyl -5 - aminosalicylic acid （AC -5 -ASA ）, and Zn2＋ in plasma were determined. Results The time that the capsules reached ascending colon and disintegrated in healthy volunteers was （ 5.80 ± 1.99 ）, （ 8.00 ± 1.63 ） h ; in patients the time was（6.80 ±3.65）, （9.75 ±2.50）h. The pharmacokinetic parameters of 5 - ASA in healthy volunteers （ n = 9 ） and patients （ n = 8 ） were as follows ： Tmax was （ 12. 33 ± 1.73 ）, （ 11.38 ± 5.72） h, respectively; Cmax was （325.72 ± 197.52）, （325.72 ± 197.52） ug . L-1, respectively; AUC0-t was（3.66 ±2.26）, （3.19 ± 1.58）mg . L-1 . h, respectively. The cumulative excretion percentage of 5 -ASA was about 9.4% in urine. Conclusion It was shown that the zinc 5 - aminosalicylate colon targetingcapsules were released in the colon, and the release and absorption were similar in the healthy volunteers and the patients groups.