Khoo Shui-Mei, Shackleford David M, Porter Christopher J H, Edwards Glenn A, Charman William N
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia.
Pharm Res. 2003 Sep;20(9):1460-5. doi: 10.1023/a:1025718513246.
To examine whether the small quantities of lipid present in unit-dose microemulsion formulations comprising medium- (C8-10) or long-chain (C18) glyceride lipids can stimulate the intestinal lymphatic transport of halofantrine (Hf), a model lymphatically transported drug.
Hf (50 mg) was administered to thoracic lymph duct- and cephalic vein-cannulated fasted greyhound dogs. Drug was formulated as a single soft gelatin capsule containing approximately 1 g of a microemulsion preconcentrate based on either medium- or long-chain glycerides. Thoracic lymph was collected, and systemic plasma samples taken over 10 h postdose.
The extent of lymphatic transport of Hf after administration of the long-chain lipid formulation was high (28.3% of dose), and significantly higher than that seen after administration of the medium-chain formulation (5.0% of dose). Plasma levels of Hf were not significantly different across the two formulations when assessed by AUC0-10h.
This is the first study to demonstrate that the small amounts of lipid present within a single lipid-based dose form can support substantial intestinal lymphatic transport in the fasted state. Furthermore, microemulsions based on long-chain glycerides appear to be more effective with respect to lymphatic transport than the equivalent medium-chain formulation.
研究包含中链（C8 - 10）或长链（C18）甘油酯脂质的单位剂量微乳制剂中存在的少量脂质是否能刺激卤泛群（一种经淋巴转运的模型药物）的肠道淋巴转运。
将卤泛群（50毫克）给予经胸导管和头静脉插管的禁食灵缇犬。药物被制成单个软胶囊，其中含有约1克基于中链或长链甘油酯的微乳预浓缩物。收集胸导管淋巴，并在给药后10小时采集全身血浆样本。
给予长链脂质制剂后卤泛群的淋巴转运程度较高（占剂量的28.3%），且显著高于给予中链制剂后的转运程度（占剂量的5.0%）。通过AUC0 - 10h评估时，两种制剂的血浆中卤泛群水平无显著差异。
这是第一项证明单一脂质剂型中存在的少量脂质能够在禁食状态下支持大量肠道淋巴转运的研究。此外，基于长链甘油酯的微乳在淋巴转运方面似乎比同等的中链制剂更有效。
