Transport of Drugs through Human Erythrocyte Membranes. Change of Transport by Introduction of Amino Group or Amino Acids in Benzoic Acid

Abstract

The transporting properties of benzoic acid (BA) and its derivatives such as hippuric acid (HPA), p-aminohippuric acid (AHPA), N-benzoyl-β-alanine (NBA), p-amino-N-benzoyl-β-alanine (ANBA), N-benzoyl-6-aminocaproic acid (NBC), p-amino-N-benzoyl-6-aminocaproic acid (ANBC), o-, m- or p-hydroxybenzoic acid (o-, m- or p-HBA) and α- or γ-resorcylic acid (α- or γ-RA) through erythrocyte membranes were examined in two aspects of the inward direction from a drug-containing medium into the erythrocyte and the outward direction from the drug-containing erythrocyte to the drug-free medium. The significant difference in the rate of transport was observed between both directions. The introduction of a few methylene groups into the amino acid moieties of BA derivatives was slower in the rate of transport than that of more methylene groups. The rate of transport was slowed down by the introduction of amino group at p-position : NBC>NBA>HPA»ANBC>ANBA>AHPA. The rate of transport in these drugs was correlated with the changes in partition coefficients. The same correlation was also observed in the drugs to which hydroxyl groups were introduced except α- or γ-RA. This transport of α- or γ-RA suggested the participation of the band 3 anion transporter protein.