Bile increases intestinal lymphatic drug transport in the fasted rat.
OBJECTIVE
This study was conducted to determine the influence of (1) the source of recruited endogenous fatty acid (FA), and (2) bile on intestinal lymphatic transport of halofantrine (Hf) in fasted rats.


METHODS
Endogenous FA output in bile, and exogenous ((14)C radiolabeled) FA, endogenous FA, and Hf transport in mesenteric lymph were determined following administration of low dose lipid formulations containing either 4 or 40 mg of exogenous FA [oleic acid (OA)] and different amounts of bile salt (BS) and lysophosphatidylcholine (LPC) to fasted rats.


RESULTS
Administration of 40 mg of OA recruited endogenous FA and Hf transport into intestinal lymph, whereas 4 mg OA did not. However, addition of BS to the 4-mg OA dose led to stimulation of endogenous FA recruitment into lymph and an increase in lymphatic transport of Hf and endogenous FA output in bile. Addition of LPC to the 4-mg OA dose (dispersed in BS) caused a substantial increase in endogenous FA transport in lymph; however, no coincident increase in either lymphatic transport of Hf or endogenous FA output in bile was observed.


CONCLUSIONS
Biliary-derived endogenous FA has a higher propensity to support lymphatic transport of Hf compared to other sources of endogenous FA. The results suggest that this is related to the disparate trafficking of these alternate sources of endogenous FA within the enterocyte.
Trevaskis
Natalie L
NL
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Porter
Christopher J H
CJ
Charman
William N
WN
D000818:Animals; D001646:Bile / Q000502:physiology*; D001692:Biological Transport; D002626:Chemistry, Pharmaceutical; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid / Q000494:pharmacology; D010616:Phenanthrenes / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D010616:Phenanthrenes; D019301:Oleic Acid; C023768:halofantrine