Rectal delivery of antiinflammatory drugs. II. The influence of basic amino acid salts on rectal absorption of diclofenac.

Abstract

Rectal absorption of diclofenac (DC) and its salts with sodium (DCNa), L-arginine (DC-Arg), L-lysine (DC-Lys), and L-histidine (DC-His) was studied in dogs, rabbits and rats. Plasma levels of unchanged DC were measured by high performance liquid chromatography. Both the bioavailability and the plasma peak level of DC-Lys were the largest among the salts studied. The bioavailability of DCNa on oral administration in terms of plasma levels of DC was observed to be much larger than after rectal administration of DC but it was of the same order as those of rectal administration of DCNa, DC-Arg, and DC-His. The extents of bioavailabilty in rabbits and in rats were similar, but considerably better than that in dogs. The irritative effects of DC salts on the rectal mucosa in rats were studied by gross and light microscopic examinations following the administration of suspensions in 1% methyl cellulose solution. DC-Arg showed the weakest irritation of the rectal mucosa, and the irritation caused by 20% suspension was equivalent to that of 5% suspension of DCNa. The protective effects of counter ions against the histological damage caused by DC to the rectal mucosa increased in the order or sodiumglysinegarginine. From these results, it appears that the basic amino acid salts of DC may be useful as rectal delivery preparations for clinical use.