摘要：The ATP-binding cassette (ABC) transporter protein subfamily B1 line (ABCB1) transporter P-glycoprotein (P-gp) plays an important role in the blood–brain barrier limiting a broad spectrum of substrates from entering the central nervous system. In the present study, the transport activity of P-gp for sertraline, desmethylsertralin, bupropion, and the major metabolites of bupropion, threo-amino alcohol (TB), erythro-amino alchhol (EB), and hydroxy metabolite (HB) was studied using an ATPase assay in expressed human P-gp membranes by measuring concentrations of inorganic P i in expressed human P-gp membranes. Verapamil was included as a positive control. The Michaelis–Menten equation was used for characterizing the kinetic data. Sertraline and desmethylsertraline showed high affinity for P-gp. The V max/ K m values of sertraline (1.6 min−1×10−3) and desmethylsertraline (1.4 min−1×10−3) were comparable with that of verapamil (1.7 min−1×10−3). Bupropion and its three metabolites showed very weak affinity for P-gp, with V max/ K m values lower than 0.01 min−1×10−3. The results of the present study indicate that sertraline and desmethylsertraline have high affinity for P-gp, whereas bupropion and its three major metabolites TB, EB, and HB have very weak affinity for P-gp. These findings may help to explain observed drug–drug interactions among antidepressants.
