Evaluation of a chylomicron flow blocking approach to investigate the intestinal lymphatic transport of lipophilic drugs

Arik Dahan, Amnon Hoffman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

162 Scopus citations


The purpose of this study was to examine the feasibility of investigating the lymphatic transport of drugs in vivo utilizing known chylomicron flow blocking substances. Vitamin D3 (0.5 mg/kg), a model lipophilic molecule, was administered to rats with blocked chylomicron flow, induced by either cycloheximide injection (3 mg/kg), colchicine injection (5 mg/kg) or intraduodenal infusion of pluronic L-81 (1 mg/h). The effect of these experimental models on the absorption of Vitamin D3 was compared to the outcomes of the mesenteric lymph duct cannulated rat model. The oral d-xylose loading test was used to verify that other intestinal absorptive functions were not affected. Colchicine treatment induced severe adverse effects whereas pluronic L-81 and the cycloheximide models did not affect other absorption pathways and did not cause apparent adverse effects. Vitamin D 3 absorption in these two models was in good correlation to the mesenteric lymph duct cannulation model (25% non-lymphatic relative bioavailability) indicating that the incorporation of the lipophilic molecule into the chylomicron is an essential step in the cascade of lymphatic absorption. Moreover, the data suggest that the drug association with the chylomicron occurs at an early stage of its assembly process. The results also specify that lymphatic absorption and portal blood absorption are separate pathways that are not affected by each other. In conclusion, the chemical blockage of chylomicron flow provides a potential approach for lymphatic transport investigation, and may elucidate processes involving in the absorption of lipophilic compounds.

Original languageAmerican English
Pages (from-to)381-388
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Issue number4
StatePublished - Mar 2005

Bibliographical note

Funding Information:
This work is a part of Arik Dahan PhD dissertation. This study was supported by the Israeli Consortium of Pharmalogica. The authors thank Dr. Josh Backon for constructive comments. A. Hoffman is affiliated with David R. Bloom Center of Pharmacy.


  • Chylomicron
  • Colchicine
  • Cycloheximide
  • Lipophilic drugs
  • Lymphatic transport
  • Pluronic L-81
  • Vitamin D


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