The colonic absorption of menaquinones was examined in rats by the in situ loop method. The overall disappearance of [14C]menaquinone-4 from the colonal loop was approximately 6% at 3 h and much slower than that of menadione. After administration of [14C]menaquinone-4 into the jejunal loop with bile, approximately 17% of unchanged menaquinone-4 was recovered in the lymph after 6 h, but none was found when the administration had been into the colonal loop. Portal absorption of menaquinone-4 from the colon was detected and the unchanged form (approximately 23% of the absorbed radioactivity) was identified in the mesenteric venous blood. When menaquinone-9 was administered into the colon, almost all was recovered from the colonal loop. No transfer of menaquinone-9 from the colon into the lymph or blood was observed at 6 h after dosing. The present observations indicate that only a part of bacterially produced menaquinones is absorbed from the colon via the portal pathway, but the absorption rates of menaquinones decrease markedly with an increase in the number of isoprenoid units.

[14C]Mepitiostane in various vehicles was administered to the small intestine of anaesthetized rats with cannulated thoracic ducts, and the effect of lipids on lymphatic absorption was examined. The extent of lymphatic absorption was greatest when administered in triolein and sesame oil, which are triglycerides of long-chain fatty acids. Absorption in the presence of other vehicles was in the order of 10% Tween 80 aqueous solution greater than monolein greater than oleic acid approximately oleic acid/monolein (2:1 mol/mol) greater than aqueous suspension. Differences between the extents of lymphatic absorption of mepitiostane in the various formulations were not due to variation in the lymph flow but to the increased secretion of chylomicron and very low density lipoproteins. During absorption of mepitiostane from the small intestine, oil affected not only the penetration into epithelium cells and the metabolism in them, but also the partition between blood and lymph.

The effects of bile and site of gastrointestinal absorption on the lymphatic absorption of the highly lipophilic drug, mepitiostane were examined using thoracic duct-cannulated rats. The lymphatic absorption from the small intestine was very small in the absence of bile compared with that when bile was present. The lymphatic absorption was greatest when drug was administered to the upper small intestine with bile, was smaller for the lower regions of the small intestine, and was negligible for the stomach and the large intestine. A correlation was observed between the extent of lymphatic absorption and the secretion of chylomicron and very low density lipoproteins after administration to various regions with or without bile. The portal absorption data of mepitiostane confirmed that site specificity occurs in the partition of drug between blood and lymph.

The action of benzyl alcohol (BA) as a major solvent of a liquid droplet dispersion ointment (LDDS), a preparation enabling excellent percutaneous absorption of drugs, was evaluated and compared with Azone and dimethyl sulfoxide (DMSO), which are known percutaneous absorption enhancers. Using a water sorption-desorption test, BA was found to increase hygroscopicity and decrease water-holding capacity to the same extent as Azone and DMSO. Differential scanning calorimetry (DSC) determination of the whole stratum corneum, and its lipids and proteins confirmed that BA and Azone act on the stratum corneum lipids while DMSO acts on its lipids and proteins. Furthermore, DSC and X-ray diffraction spectrum determinations of lipids in the stratum corneum suggest that the action of BA is moderate and reversible. The effect of BA may be one of the factors underlying the high percutaneous absorption found with LDDS.