SOFT DRUGS .18. ORAL AND RECTAL DELIVERY OF LOTEPREDNOL ETABONATE, A NOVEL SOFT CORTICOSTEROID, IN RATS FOR SAFER TREATMENT OF GASTROINTESTINAL INFLAMMATION
SOFT DRUGS .18. ORAL AND RECTAL DELIVERY OF LOTEPREDNOL ETABONATE, A NOVEL SOFT CORTICOSTEROID, IN RATS FOR SAFER TREATMENT OF GASTROINTESTINAL INFLAMMATION
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DOI：
10.1023/a:1016213121069
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发表时间：
1995-06-01
影响因子：
3.7
通讯作者：
WU, WM
中科院分区：
文献类型：
--
作者：
BODOR, N;MURAKAMI, T;WU, WM
目的.作为一种安全的抗炎皮质类固醇，在大鼠中研究了依碳酸氯替泼诺（LE）经口和直肠给药治疗胃肠道炎症的效用。方法.在体内，口服LE溶液和悬浮液（20 mg/kg），并将各种LE制剂（溶液、悬浮液和栓剂）应用于直肠环（每环0.2 mg）。在体外，各种胃肠道组织被用来研究LE的稳定性和分配。结果口服LE溶液后，由于吸收和/或分解，LE有效到达上消化道，但未到达结肠。在悬浮液中，LE在8小时内到达大部分胃肠道（直肠除外），几乎没有吸收。直肠给药后，LE在直肠袢中保持完整，持续时间超过5小时，消失速度缓慢，但LE在直肠膜上有一定程度的分布。口服和直肠给药后血浆中LE及其非活性代谢产物的浓度在实验期间的任何时间均低于检测限（0.1 μ g/ml）。在体外，LE溶液在胃中稳定，但在盲肠中不稳定，这是由于盲肠驻留微生物植物群的水解。在溶液中，LE有效地分布到粘膜中（约2.5类似于4.0 μ g/g组织）。结论.结果表明，LE可以在胃肠道中口服或直肠递送，用于炎症性肠病的局部治疗。
Purpose. As a safe anti-inflammatory corticosteroid, the utility of loteprednol etabonate (LE) for the treatment of gastrointestinal inflammation, via oral and rectal administration, was investigated in rats. Methods. In vivo, LE solution and suspension were orally administered (20 mg/kg), and various LE preparations (solution, suspension and suppository) were applied in rectal loops (0.2 mg per loop). In vitro, various GI tissues were used to study the stability and partition of LE. Results. After oral administration of LE solution, LE reached the upper GI tract effectively, but not the colon, due to absorption and/or decomposition. In suspension, LE reached most of the GI tract (except rectum) in 8 hr and showed little absorption. After rectal applications, LE remained intact in the rectal loop for more than five hours with a slow rate of disappearance, however, LE distributed in the rectal membrane to some extent. The concentrations of LE and its inactive metabolites in plasma after both oral and rectal administrations were lower than the detection limit (0.1 mu g/ml) at anytime during the experiments. In vitro, LE in solution was stable in stomach, but not in cecum, due to the hydrolysis by the cecal resident micro flora. In solution, LE distributed into the mucosal membranes efficiently (about 2.5 similar to 4.0 mu g/g tissue). Conclusions. The results suggest that LE can be orally or rectally delivered in the GI tract for the topical treatment of the inflammatory bowel disease.