Sertraline and Its Metabolite Desmethylsertraline, but not Bupropion or Its Three Major Metabolites, Have High Affinity for P-Glycoprotein
| Autor: | Hao Jie Zhu, Bryan Bradford Gibson, Carl Lindsay DeVane, Jennifer L. Donovan, Jun Sheng Wang, John S. Markowitz |
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| Rok vydání: | 2008 |
| Předmět: |
ATPase
Metabolite Pharmaceutical Science ATP-binding cassette transporter In Vitro Techniques Pharmacology Article chemistry.chemical_compound Sertraline medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Bupropion P-glycoprotein Adenosine Triphosphatases biology Desmethylsertraline General Medicine Antidepressive Agents chemistry Blood-Brain Barrier Data Interpretation Statistical biology.protein Antidepressive Agents Second-Generation Verapamil Algorithms Protein Binding medicine.drug |
| Zdroj: | Biological & Pharmaceutical Bulletin. 31:231-234 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | 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, desmethylsertraline, bupropion, and the major metabolites of bupropion, threo-amino alcohol (TB), erythro-amino alcohol (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) x 10(-3)) and desmethylsertraline (1.4 min(-1) x 10(-3)) were comparable with that of verapamil (1.7 min(-1) x 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) x 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. |
| Databáze: | OpenAIRE |
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