Holm René, Porter Christopher J H, Müllertz Anette, Kristensen Henning G, Charman William N
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark.
Pharm Res. 2002 Sep;19(9):1354-61. doi: 10.1023/a:1020311127328.
To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats.
Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration of halofantrine in blood and lymph samples was analyzed by HPLC.
Both the lymphatic transport and the total absorption of halofantrine were enhanced by the use the MLM triglyceride. The estimated total absorption of halofantrine in the lymph cannulated animals was higher than in the nonlymph cannulated animals, and this was most pronounced for the animals dosed with the structured triglycerides.
Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.
比较甘油三酯载体分子结构对清醒大鼠中卤泛群肠道淋巴转运及全身吸收的影响。
对清醒、已插管引流淋巴液和未插管引流淋巴液的大鼠口服给予三种结构不同的甘油三酯；葵花籽油，以及两种在甘油主链上含有不同比例和位置的中链（M）和长链（L）脂肪酸的结构化甘油三酯。这两种结构化甘油三酯缩写为MLM和LML以反映其在甘油上的结构位置。通过高效液相色谱法分析血液和淋巴液样本中卤泛群的浓度。
使用MLM甘油三酯可增强卤泛群的淋巴转运及总吸收。插管引流淋巴液动物中卤泛群的估计总吸收高于未插管引流淋巴液的动物，这在给予结构化甘油三酯的动物中最为明显。
以MLM作为载体可增加卤泛群的门静脉吸收，并且与葵花籽油相比，可导致相似的淋巴转运水平。当以MLM甘油三酯给药后卤泛群在血液中的吸收加淋巴转运来评估总吸收时，其高于以葵花籽油给药后的总吸收。
