h e intestinal absorption of certain water-soluble acidic dyes (bromthymol blue, methyl orange, and e0sine-B) and some of their lipoid-soluble complexes has been investigated. T h e results of these studies show that the ap arent lipoid-water paniplexes investigated. tion coefficient does not reflect the intestinal absorption c g aracteristics of the com-HE POTENTIALITIES of complex formation as a T means of enhancing t h e gastrointestinal absorption of drugs are largely unexplored. The concept of a reversible reaction between a substrate and a carrier, resulting in the formation of a complex capable of moving relatively rapiifly across a biological membrane, has proved useful in the quantitative interpretation of active transport processes (1). Attempts to isolate such carriers have resulted (in the case of investigations of the sugar-transfer system) in the isolation of phospholipids capable of forming lipid-soluble complexes with glucose and other mono-saccharides (2). Since the gastrointestinal absorption of most drugs proceeds b y passive diffusion of nonionized molecules, and since their rates of absorption (from solution) usually increase with increasing lipoid-water partition coefficient (3), i t is of interest to investigate the possibility of enhancing the absorption of certain drugs b y formation of more lipid-soluble complexes. This report, one of a series on the effect of complex formation on drug absorption (4), deals with the intestinal absorption rate of certain water-soluble acidic dyes a n d their lipoid-soluble complexes.
EXPERIMENTAL
Materiais,-Bromthymol blue (Nutritional Biochemicals Corp., lot No. 5152), methyl orange (Nutritional Biochemicals Corp., lot No. 4125), eosine-B (Allied Chemical Corp., certification No. 25), diphenhydramine hydrochloride.1 2,4-dinitrophenol (Mann Research Laboratories, Inc.). All other materials were of U.S.P. or N.F. grade.
Preparation of Solutiotx-The buffer solutions used as the solvent for the dyes and complexing agents consisted of 12 parts, by volume, of Krebs-Ringer solution (5) and 1 part, by volume, of either 0.1 M phosphate or 0.1 M acetate buffer. The pH