Transport of drugs through human erythrocyte membrane. Structure-activity relationship of benzoic acid and its derivatives between membrane transport and partition coefficient]

The transport properties of benzoic acid and its eighteen derivatives such as o-, m- or p-hydroxybenzoic acid (o-, m- or p-HBA), aminobenzoic acid (o-, m- or p-ABA), toluic acid (o-, m- or p-TA), fluorobenzoic acid (o-, m- or p-FBA), chlorobenzoic acid (o-, m- or p-CBA) and bromobenzoic acid (o-, m- or p-BBA) through human erythrocyte membranes were examined. The drugs having a hydrophilic ortho-substituent and those having a hydrophobic meta- or para-substituent showed higher transport. The ratio of free drugs in erythrocytes, fuR, did not relate to the partition coefficient (P). However, fuM (the ratio of free drugs in the plasma) and Kp (the ratio of partition between erythrocytes and plasma) related to the P: fuM = -0.3128 x log P + 0.9727 (R2 = 0.8722***), Kp = -0.2558 x log P + 0.8642 (R2 = 0.8413***). In p-nitrophenol-glycosides, the fuM and the Kp that were predicted from these equations were compatible with the experimental results. It was suggested from these results that the fuM and the Kp may be predictable from the P.