Prasad Y V Rama, Puthli S P, Eaimtrakarn Sudarat, Ishida Makoto, Yoshikawa Yukako, Shibata Nobuhito, Takada Kanji
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan.
Int J Pharm. 2003 Jan 2;250(1):181-90. doi: 10.1016/s0378-5173(02)00544-6.
Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic used for the treatment of infections caused by methicillin-resistant staphylococci. It is water soluble, having a high molecular weight, and poorly absorbed from the gastrointestinal tract. Mixtures of VCM with Labrasol and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared to improve oral absorption of VCM. Administration of VCM solution to rat ileum at a dose of 20 mg/kg did not result in detectable plasma VCM concentration. Formulation containing 50% of Labrasol resulted in a Cmax value of 5.86+/-0.97 microg/ml and an AUC(0-6h) value of 16.06+/-1.78 microgh/ml. Addition of TPGS to VCM solution at 12.5% concentration also increased the plasma VCM concentration with a Cmax value of 4.98+/-0.45 microg/ml. But the AUC(0-6 h) (9.87+/-1.90 microgh/ml) was significantly lower than that obtained with Labrasol. The addition of 5.0 and 25.0% TPGS to solutions of VCM containing 50% of Labrasol did not result in any significant increase either in Cmax or AUC(0-6 h) of VCM. Whereas the addition of 12.5% of TPGS has resulted in an increase in Cmax and AUC(0-6 h) by 2.2 and 2.4 times, respectively, suggesting that this concentration of 50% Labrasol and 12.5% TPGS (1:0.25) was optimum for improving intestinal absorption of VCM. A dose dependent decrease in the Cmax and AUC(0-6 h) values was observed when the dose of absorption enhancers was decreased by 50% with formulation containing Labrasol and TPGS in 1:0.25 ratio. The results of the study indicate that formulations containing Labrasol and TPGS improve intestinal absorption of hydrophilic macromolecular drug, VCM.
盐酸万古霉素（VCM）是一种糖肽类抗生素，用于治疗耐甲氧西林葡萄球菌引起的感染。它可溶于水，分子量高，胃肠道吸收差。制备了VCM与Labrasol和聚乙二醇1000维生素E琥珀酸酯（TPGS）的混合物，以改善VCM的口服吸收。以20mg/kg的剂量向大鼠回肠给药VCM溶液，未检测到血浆VCM浓度。含有50%Labrasol的制剂的Cmax值为5.86±0.97μg/ml，AUC(0-6h)值为16.06±1.78μg·h/ml。以12.5%的浓度向VCM溶液中添加TPGS也提高了血浆VCM浓度，Cmax值为4.98±0.45μg/ml。但AUC(0-6 h)（9.87±1.90μg·h/ml）显著低于使用Labrasol时的值。向含有50%Labrasol的VCM溶液中添加5.0%和25.0%的TPGS，VCM的Cmax或AUC(0-6 h)均未显著增加。而添加12.5%的TPGS使Cmax和AUC(0-6 h)分别增加了2.2倍和2.4倍，表明50%Labrasol和12.5%TPGS（1:0.25）的该浓度最适合改善VCM的肠道吸收。当吸收促进剂的剂量降低50%时，使用1:0.25比例的Labrasol和TPGS制剂，Cmax和AUC(0-6 h)值呈剂量依赖性降低。研究结果表明，含有Labrasol和TPGS的制剂可改善亲水性大分子药物VCM的肠道吸收。
