The influence of concentration of two salicylate derivatives on rectal insulin absorption enhancement.

3,5-Diiodosalicylate sodium (DIS), a highly lipophilic salicylate, was evaluated against 5-methoxysalicylate sodium (MS) as a potential adjuvant absorption promoter for rectal insulin delivery. Comparative blood glucose measurements were made using the two adjuvants under identical conditions as promoters of rectal insulin absorption in rats. Concentrations of DIS greater than and including 0.1 M produced an unexpected, progressive decrease in adjuvant activity as determined by a decline in observed hypoglycaemic response. This was not due to formation of an insulin-DIS complex. The adjuvant MS produced a classical, sigmoidal log-dose response curve. Possible reasons for the occurrence of the DIS optimum phenomenon are discussed as well as are the observed differences in adjuvant potency of these agents in a propylene glycol-containing vehicle.