IMPROVEMENT OF THE RECTAL BIOAVAILABILITY OF LATAMOXEF SODIUM BY ADJUVANTS FOLLOWING ADMINISTRATION OF A SUPPOSITORY

The absorption of an antibiotic, latamoxef sodium (LMOX), following th e rectal administration of a suppository containing adjuvants was inve stigated. A lipophilic base (Witepsol H15) was used. The rectal absorp tion of LMOX following the administration of a suppository without adj uvants was very low. Diclofenac sodium (DF) was used as an absorption promoter; it enhances rectal membrane permeability. The blood level of LMOX following the addition of DF(10 mg) to the base was increased on ly about 1.3-fold compared with that achieved with LMOX alone (differe nce not significant); even with a higher dose of DF, the absorption of LMOX,pas not sufficient. The release rate of LMOX from the base was s low. When Tween 80, a non-ionic surfactant, was added to improve the r elease rate of LMOX, the rate was sufficiently increased. The rectal a bsorption of LMOX: on the addition of both Tween 80 and DF was markedl y increased compared to that achieved with LMOX alone or with DF. Thes e results indicate that the rectal absorption of LMOX after administra tion by a suppository was sufficiently improved by enhancing both the release rate from the base and the membrane permeability of the rectum . Lymphatic uptake and blood levels of LMOX were also investigated aft er the rectal administration of the LMOX preparation containing both T ween 80 and DF; the lymphatic uptake of LMOX was significantly enhance d compared with the LMOX preparation in which only DF was used as an a djuvant. The mechanism whereby adjuvants lead to the absorption of a n on-absorbable drug, and the subsequent drug transportation routes thro ugh the membrane are discussed.