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5121522 
Journal Article 
Uptake of lipophilic drugs by plasma derived isolated chylomicrons: linear correlation with intestinal lymphatic bioavailability 
Gershkovich, P; Hoffman, A 
2005 
Yes 
European Journal of Pharmaceutical Sciences
ISSN: 0928-0987
EISSN: 1879-0720 
26 
5 
394-404 
English 
16140514 
WOS:000233522900004 
Association of a drug with chylomicrons in the enterocyte is an essential step in the lymphatic absorption pathway. In this article, the uptake of lipophilic compounds by chylomicrons ex vivo was compared to the corresponding intestinal lymphatic bioavailability reported in rats in order to elucidate the degree of correlation and to evaluate the utilization of this correlation as a predictive measurement of the lymphatic bioavailability potential of lipophilic drugs. Nine lipophilic compounds (Vitamin D(3), Vitamin E, halofantrine, probucol, diazepam, testosterone, cyclosporin A, benzo[a]pyrene and p,p'-DDT) at a concentration of 1.75 x 10(-6)M were incubated for 1h with chylomicron emulsion separated from rat blood. A strong linear correlation was found between the degree of association of compounds with chylomicrons ex vivo and the lymphatic transport reported in rats (r(2)=0.94, P<0.0001), whereas logP and solubility in long chain triglycerides showed only moderate correlation with lymphatic bioavailability. The linear correlation between the degree of uptake of compounds by isolated chylomicrons and intestinal lymphatic transport suggests that the two processes are governed by similar factors. Thus, the degree of association of lipophilic compounds with isolated chylomicrons can be used as a simple screening model for estimation of intestinal lymphatic transport potential of drug molecules. This approach is important in view of the practical difficulties in direct determination of the lymphatic bioavailability in vivo. 
Absorption; Chylomicrons; Ex vivo; Lipophilic drugs; log P; Lymphatic transport