A novel emulsifier, Labrasol, enhances gastrointestinal absorption of gentamicin
A novel emulsifier, Labrasol, enhances gastrointestinal absorption of gentamicin
复制标题
DOI：
10.1016/s0024-3205(01)01375-3
复制
发表时间：
2001-11-02
期刊：
影响因子：
6.1
通讯作者：
Takada, K
中科院分区：
文献类型：
--
作者：
Hu, ZP;Tawa, R;Takada, K
庆大霉素(GM)是一种重要的氨基糖苷类抗生素，用于治疗由广谱的革兰氏阴性杆菌和革兰氏阳性球菌引起的感染。作为一类，氨基糖苷类药物从胃肠道吸收较差，通常用作注射和外用制剂。本研究旨在探讨新型乳化剂拉布拉索尔对大鼠胃肠道中GM吸收的影响。将GM制剂制成生理盐水或Labrasol微乳，分别给大鼠小肠和结肠给药。肠道给药后血浆GM水平与静脉给药后血浆GM水平进行比较。行政管理。5 mg/kg剂量的含有拉布拉索尔的GM制剂，1ml/kg，结肠给药，平均AUC值为21.179+/-1.374 mug×h/ml，而静脉注射给药的平均AUC值为7.813+/-0.105 mug xh/ml。GM给药，1 mg/kg。拉布拉索尔制剂的绝对生物利用度为54.2%。Labrasol通过形成微乳促进GM在大鼠结肠粘膜的转运，微乳的BA高于其他表面活性剂(Tween80为8.4%，Transcutol P为3.4%)。此外，体外渗透研究表明，拉布拉索尔还能抑制肠道的分泌转运。拉布拉索尔的作用归因于(1)促进GM从肠腔进入体循环和(2)抑制GM从肠细胞外流到GI腔。(C)2001 Elsevier Science Inc.保留所有权利。
Gentamicin (GM) is an important aminoglycoside antibiotic for the treatment of infections caused by a wide spectrum of aerobic gram-negative bacilli and gram-positive cocci. As a class, the aminoglycosides are poorly absorbed from the gastrointestinal (GI) tract and are commonly used as injectable and topical preparations. This study was aimed at finding the effect of a novel emulsifier, Labrasol, on the absorption of GM from the GI tract of rats. GM formulations were prepared, either as saline solution or as Labrasol microemulsions, and were administrated to rat small intestine and colon. Plasma GM levels following intestinal application were compared to those obtained with intravenous (i.v.) administration. A 5 mg/kg dose of GM preparation containing Labrasol, 1 ml/kg, administrated into colon resulted in the mean AUC of 21.179 +/- 1.374 mug x h/ml, compared to 7.813 +/- 0.105 mug x h/ml obtained with i.v. administration of GM, I mg/kg. The absolute bioavailability (BA) of the Labrasol preparation was 54.2%. Labrasol facilitates the transmucosal delivery of GM from rat colon by forming microemulsions, and the BA obtained with Labrasol microemulsion was higher than with other surfactants (8.4% for Tween 80 and 3.4% for Transcutol P). Additionally, in vitro permeation studies demonstrated that Labrasol also inhibited the intestinal secretory transport. The effect of Labrasol is ascribed to both (1) enhanced GM absorption from the GI lumen into the systemic circulation and (2) inhibition of efflux of GM from the enterocytes to the GI lumen. (C) 2001 Elsevier Science Inc. All rights reserved.