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  • Title: Intestinal lymphatic transport of halofantrine in rats assessed using a chylomicron flow blocking approach: the influence of polysorbate 60 and 80.
    Author: Lind ML, Jacobsen J, Holm R, Müllertz A.
    Journal: Eur J Pharm Sci; 2008 Oct 02; 35(3):211-8. PubMed ID: 18675904.
    Abstract:
    The aim of the study was to examine the effects of polysorbate 60 and 80 on intestinal lymphatic transport of a poorly water-soluble compound, halofantrine, using a chylomicron flow blocking approach in rats. Male Sprague-Dawley rats were pretreated intraperitoneally with 3.0 mg/kg cycloheximide or saline. One hour later, rats were dosed with 6.7 mg/kg halofantrine in 0.4 or 1.0 g/kg polysorbate 60 or 80, 0.33 g/kg soybean oil or 0.33 g/kg soybean oil+1.0 g/kg polysorbate 80 by gavage, and plasma samples were collected. The fraction of halofantrine transported to the lymphatic system was determined as the difference between the bioavailability in saline-pretreated rats and cycloheximide-pretreated rats. No significant differences in halofantrine transport to the systemic blood and in the deduced lymphatic transport were observed between the two polysorbates, at the tested dosages. The lymphatic transport of halofantrine was the same whether dosing with polysorbate 60, polysorbate 80 or soybean oil; accordingly both surfactants can be used as lymphotropic carriers. Furthermore, there was a good correlation between the halofantrine transport to blood and lymphatics in the chylomicron flow blocking model and published results from the mesenteric lymph-cannulated model.
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