Renata D'Incà, Martina Paccagnella, Romilda Cardin, Surajit Pathak, Giacomo Carlo Sturniolo, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35127 Padova, Italy.
World J Gastroenterol. 2013 Sep 14;19(34):5665-70. doi: 10.3748/wjg.v19.i34.5665.
To compare the mucosal concentrations of 5-aminosalicylic acid (5-ASA) resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.
The study included 130 inflammatory bowel disease (IBD) patients receiving 5-ASA as pH-dependent-release formulations (73 patients), time-dependent-release formulations (11 patients), or pro-drugs (18 patients). In addition, 28 patients were receiving topical treatment (2-4 g/d) with pH-dependent-release formulations. Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy. The 5-ASA concentrations (ng/mg) were measured in tissue homogenates using high-pressure liquid chromatography with electrochemical detection. The t test and Mann-Whitney test, when appropriate, were used for statistical analysis.
Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA (51.75 ± 5.72 ng/mg) compared with patients receiving pro-drugs (33.35 ± 5.78 ng/mg, P = 0.01) or time-dependent-release formulations (38.24 ± 5.53 ng/mg, P = 0.04). Patients with endoscopic remission had significantly higher mucosal concentrations of 5-ASA than patients with active disease (60.14 ± 7.95 ng/mg vs 35.66 ± 5.68 ng/mg, P = 0.02). Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation (67.53 ± 9.22 ng/mg vs 35.53 ± 5.63 ng/mg, P < 0.001). Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone (72.33 ± 11.23 ng/mg vs 51.75 ± 5.72 ng/mg, P = 0.03).
IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation, and the highest mean concentration was achieved using pH-dependent-release formulations.
比较不同药物制剂的 5-氨基水杨酸（5-ASA）黏膜浓度，并分析炎症对黏膜浓度的影响。
本研究纳入了 130 例接受 5-ASA 治疗的炎症性肠病（IBD）患者，其中 73 例患者接受 pH 依赖性释放制剂治疗，11 例患者接受时间依赖性释放制剂治疗，18 例患者接受前体药物治疗。此外，28 例患者接受 pH 依赖性释放制剂局部治疗（2-4 g/d）。结肠镜检查时，从乙状结肠区域采集内镜活检标本。采用高压液相色谱电化学检测法测定组织匀浆中的 5-ASA 浓度（ng/mg）。采用 t 检验和 Mann-Whitney 检验进行统计学分析。
接受 pH 依赖性释放制剂治疗的患者黏膜 5-ASA 浓度显著高于接受前体药物（33.35±5.78 ng/mg，P=0.01）或时间依赖性释放制剂（38.24±5.53 ng/mg，P=0.04）治疗的患者。内镜缓解患者的黏膜 5-ASA 浓度显著高于活动期疾病患者（60.14±7.95 ng/mg 比 35.66±5.68 ng/mg，P=0.02）。当我们比较组织学缓解和活动期组织学炎症患者时，也得到了类似的结果（67.53±9.22 ng/mg 比 35.53±5.63 ng/mg，P<0.001）。接受口服和局部联合治疗的患者黏膜 5-ASA 浓度显著高于仅接受 pH 依赖性释放制剂治疗的患者（72.33±11.23 ng/mg 比 51.75±5.72 ng/mg，P=0.03）。
IBD 患者的黏膜 5-ASA 浓度存在显著的变异性，取决于制剂类型，其中 pH 依赖性释放制剂的平均浓度最高。
