Albumin binding and hydrophobic character of promazine and chlorpromazine metabolites.

Abstract

1. The binding of didesmethylpromazine, promazine N-oxide, 2-hydroxypromazine, promazine sulfoxide, monodesmethylpromazine sulfoxide, didesmethylchlorpromazine, chlorpromazine N-oxide, and chlorpromazine sulfoxide to bovine serum albumin was determined by means of sephadex gel filtration. 2. The albumin binding of these substances was characterized by the following parameters: the percentage α of free substance, the percentage β of bound substance, the binding constants K1, k+ and m, the number of binding sites per albumin molecule, and the free binding energy ΔFo. 3. The partition coefficients between n-octanol and buffer solution, pH 7.40, were measured for the above mentioned metabolites of promazine and chlorpromazine. All metabolites were more hydrophilic than their parent compounds. The chlorine substituted metabolites were always more hydrophobic than the corresponding promazine metabolites. 4. The pharmacokinetic relevance of these results as well as their support for the idea of a phenothiazine-albumin complex were discussed.