Rectal delivery of antiinflammatory drugs. I. The influence of antiinflammatory drugs on rectal absorption of .BETA.-lactam antibiotics.

Abstract

The effects of non-steroid antiinflammatory (NSAI) drugs on the rectal membrane were studied by measuring the change in the rectal absorption of ampicillin and cephalothin. All the NSAI drugs studied the rectal absorption of antibiotics which were not able to permeate readily through the rectal membrane in the absence of NSAI drugs. The optimum concentrations of NSAI drugs as adjuvants in triglyceride suppositories containing 10% ampicillin sodium were 1.5% for indomethacin sodium and diclofenac sodium, 5% for mepirizole, 7.5% for phenylbutazone and 10% for sodium salicylate. These concentrations of NSAI drugs were used in a study of the promoting efficacy of the drugs as adjuvants for the rectal absorption of antibiotics. The promoting efects of adjuvants in dogs were inferior to those in rabbits. In simultaneous measurements of NSAI drugs and antibiotic, the absorption of antibiotic started at the early stages after the administration of suppositories and the peak blood level was reached while the blood concentration of NSAI drug was still increasing. Evidently, the NSAI drugs made the mucosal barrier leaky to H2O-soluble antibiotics at the early stages of permeation of the NSAI drugs through the rectal membrane, and the barrier rapidly recovered its normal properties even while the permeation of NSAI drug was continuing and a considerable amount of antibiotic still remained in the rectal cavity. A linear correlation between the enhanced absorption of antibiotics and the antiinflammatory activity of NSAI drugs against carrageenan-induced edema was observed.