An experimental system designed to study the in situ intestinal lymphatic transport of lipophilic drugs in anesthetized rats

Abstract

An experimental system has been developed that enables an estimate of the lymphatic transport of DDT (1,1-bis( p-chlorophenyl)-2,2,2-trichloroet p, p-DDT) by the small intestine. The system has been designed after consideration and evaluation of the effect of fasting, surgical methodology and the site of administration of drug and lipid vehicle on the lymphatic transport of DDT in the anesthetized rat. The fasting state of the animal, and the methodology used in the estimation of transport has a large effect on the lymphatic appearance of intraduodenally administered DDT. Additionally a simple spectrophotometric method has been developed to estimate lipid transport by the intestinal lymphatic system. The total lipid transported was used as an indication of the chylomicron flux in the intestinal lymph. The appearance of DDT in the intestinal lymphatics was quantitated after administration in 200 μl of either peanut oil or oleic acid. There were statistically significant differences in the amount of DDT transported into the lymph over the post-dosing period when the DDT was administered in the two vehicles. The kinetics of lymphatic DDT transport were also lipid vehicle dependent. On comparing DDT transport with chylomicron or lymph flow, chylomicron flux, and not lymph flow, was the major determinate of lymphatic DDT transport.