The relationship of salicylate lipophilicity to rectal insulin absorption enhancement and relative lymphatic uptake

The sodium salts of the 3, 5-dichloro, 3, 5-dibromo-, 3, 5-diiodo-, and 5-methoxy-analogs of salicylic acid have been evaluated as enhancers of rectal insulin absorption. A relationship was found between adjuvant potency and relative lipophilicity. Maximal adjuvant activity was obtained with 0.1 M 3, 5-dichlorosalicylate. Higher concentrations (0.15 M) of 3, 5-diiodosalicylate produced a decline in adjuvant activity, which may be associated with extraction of specific cellular proteins. This may indicate the existence of an optimal salicylate lipophilicity for adjuvant efficacy. Relative adjuvant activity was found to be related to the lymph : plasma absorption ratio of [125I] insulin. Lymphatic uptake of insulin was not related to lymph flow rate.