5-ASA不同药物制剂在溃疡性结肠炎患者肠黏膜中浓度的对比研究

Colonic mucosal concentrations of 5-ASA resulting from different pharmaceutical formulations in ulcerative colitis

目的比较5-ASA不同药物制剂治疗溃疡性结肠炎(ulcerative colitis,UC)患者肠黏膜中浓度的差异。方法纳入我院133例UC患者,按治疗分为四组:A组(pH依赖的5-ASA)68例,B组(时间依赖的5-ASA)14例,C组(5-ASA前体)30例,D组(pH依赖的5-ASA,口服联合局部用药)21例,常规行肠镜检查并于乙状结肠区取组织活检,采用高压液相色谱法分析比较肠黏膜中5-ASA药物浓度。结果①A组肠黏膜5-ASA浓度明显高于B组及C组(P<0.05);②内镜下缓解期的UC患者肠黏膜5-ASA浓度明显高于活动期患者[(61.02±7.11)ng/mg vs(36.16±6.28)ng/mg,P=0.03],组织学炎症缓解的UC患者肠黏膜5-ASA浓度明显高于炎症活动的患者[(66.68±8.95)ng/mg vs(34.98±5.61)ng/mg,P<0.001];③口服联合局部用药(灌肠)的UC患者肠黏膜5-ASA浓度明显高于单独口服用药的患者[(72.55±10.89)ng/mg vs(52.21±6.78)ng/mg,P=0.03]。结论 5-ASA治疗UC患者,pH依赖性的5-ASA易获得较高的药物浓度,且口服联合局部用药效果更佳。

Objective To compare the mucosal concentrations of 5-aminosalicylicacid （5-ASA） resulting from dif- ferent pharmaceutical formulations in ulcerative colitis （UC） and to analyze the i±nfluence of the mucosal concentrations on inflammation. Methods The study included 133 ulcerative colitis （UC） patients from Xianning City Central Hospi- tal, the patients were divided into four groups, group A received 5-ASA as pH-dependent-release formulations （68 pa- tients）, group B received time-dependent-release formulations （14 patients） , group C received pro-drugs （30 patients） and group D received topical and syetemie treatment with pH-dependent-release formulations （21 patients）. Endoscopic biopsies were obtained from the sigmoid region during the eolonoseopy. The 5-ASA concentrations were measured in tis- sue homogenates by high-pressure liquid chromatography with electrochemical detection. Results Patients of group A showed significantly higher mucosal concentrations of 5-ASA than that of group B and group C （P 〈 0.05）. Patients with endoscopic remission had significantly higher mucosal concentrations of 5-ASA than that of patients with active dis- ease [ （61.02 ± 7.11 ） ng/mg vs （36.16 ±6.28） ng/mg, P = 0.03 ]. Similar results were obtained when compared pa- tients with the histological appearance of remission and patients with active histological inflammation [ （66.68 ± 8.95） ng/mg vs （34.98 ± 5.61 ） ng/mg, P 〈 0. 001 ]. Significantly higher mueosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments compared with patients who received oral treatment with pH-de- pendent-release formulations alone[ （72.55 ± 10.89） ng/mgvs （52.21 ±6.78） ng/mg, P=0.03]. Conclusion UC patients using pH-dependent-release formulatins show the highest mean concentration and it is better both oral and topi- cal treatments.