Lymphatic transport of griseofulvin in the rat and the possible factors determining the extent of lymphatic absorption.

Abstract

Lymphatic and plasma levels of griseofulvin were determined in the rat after intraluminal administration as an oil-in-water emulsion dosage form. Compared with oral administration, peak plasma levels are attained in a very short time. This finding supports the proposed mechanism that the bioavailability of orally administered griseofulvin was improved by inhibition of gastric motility. Although peak lymphatic level is reached more slowly than the peak plasma level, griseofulvin peak concentration is almost as high, suggesting that the lymphatic appearance of griseofulvin is due to its distribution in the body water, of which lymph is a part. The possible factors determining the extent of lymphatic absorption of lipid-soluble compounds have been discussed with the special reference to their dissolution characteristics in vitro. Two groups (lymph/plasma>1 and lymph/plasmag1) related to the ratio of dissolution rates in an oil-in-water emulsion and in 6% BSA solution are distinguished. It is suggested that one of the major factors determining the extent of lymphatic absorption is the affinity with carriers in the portal route rather than that with lymphatic ones.