Imipramine and its major unconjugated metabolites have been characterized by their buccal absorption, partition between water and organic solvents—both as a function of pH—and their ionization constants. Furthermore new data are presented on the selective passage of these compounds across the blood brain barrier and on renal excretion as a function of urinary pH in the rat. The shape of the curves of buccal absorption against pH is characteristic for each one of the ten compounds tested and reflects both lipophility of the unionized compound and the pK value. The value of the buccal absorption test for interpreting or predicting pharmacokinetic behaviour of a drug is emphasized.

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