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Abstract

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.

A Mouse Model to Evaluate the Impact of Species, Sex, and Lipid Load on Lymphatic Drug Transport

“…In Part 2, the lymphatic transport of triglyceride and halofantrine in male mice was compared to previous data collected in mesenteric lymph duct cannulated rats (20,21,26–28) and thoracic lymph duct cannulated dogs (9,29) administered various long chain lipid (oleic acid, olive oil, soybean oil) doses. Additional data was also obtained after administration of 18.1 mg/kg long chain lipid to mesenteric lymph duct cannulated anaesthetised male and female rats, and conscious male rats to provide a complete set of data across species at this dose.…”

“…The oral bioavailability of halofantrine was calculated after administration to anaesthetised or conscious mice and rats via comparison of plasma AUCs after oral dosing with 18.1 mg/kg long chain lipid and after IV dosing. The mouse and rat data was compared to previous data obtained after administration of halofantrine with 18.1 mg/kg long chain lipid to thoracic lymph duct cannulated conscious greyhound dogs (9,29). …”

Intestinal Lymphatic Transport Enhances the Post-Prandial Oral Bioavailability of a Novel Cannabinoid Receptor Agonist Via Avoidance of First-Pass Metabolism

“…Following a 10-fold dilution of lymph samples in Milli-Q water, triglyceride (TG) concentrations were determined using a clinical chemistry analyser (Roche Cobas Mira, Switzerland) and a commercial enzyme-based colorimetric assay kit (Boehringer Mannheim, Germany) as described previously (18).…”

“…Whilst lymphatic transport has been demonstrated to be a significant absorption pathway for only relatively few marketed drugs (1), empirical evidence suggests that the number of drug development candidates with potential lymphatic involvement is increasing (due in large part to the well acknowledged trend toward the discovery of more lipophilic drug candidates) (17). An early understanding of the potential involvement of lymphatic transport in oral bioavailability during drug development is therefore of increasing importance, given that alterations to lymphatic transport may impact on exposure and that the extent of lymphatic transport is highly formulation dependent (18). CRA13 (Fig.…”

Evaluation of Intestinal Absorption of Ginsenoside Rg1 Incorporated in Microemulison Using Parallel Artificial Membrane Permeability Assay

“…Hitherto, mechanisms of enhanced oral absorption for lipophilic drug offered by o/w ME have been comparatively clarified, such as improved solubility and dissolution, [26][27][28][29] increased intestinal membrane permeability, 32) or accelerated transport of lipophilic drug through the routes of lymph. 33) However, it is still largely unclear for w/o ME, one of the primary mechanisms is considered to be releated to its increased intestinal membrane permeability of drug, the medium chain length fatty acid lipid components and other bioenhancers such as phosphatidylcholine (PC) that are commonly consisted in the w/o MEs have been shown to enhance transmemebrane passage of drug across the digestive tract, thus improving the bioavailability. 24,34) It was further confirmed in the present study as shown in Table 3, P e (D-MEs) are mostly higher than that of drug solution (Rg 1 concentration 11 mg/ml) (8.61Ϯ2.26ϫ10 Ϫ8 cm/s), as well as rat in vitro permeability model (everted intestinal sac), suggesting the increased membrane permeability of Rg 1 offered by w/o ME.…”