Kinetic Characterization of Sulfasalazine Transport by Human ATP-Binding Cassette G2

• Published in: Biological & Pharmaceutical Bulletin Vol. 32; no. 3; pp. 497 - 499
• Main Authors: Jani, Márton, Szabó, Pál, Kis, Emese, Molnár, Éva, Glavinas, Hristos, Krajcsi, Péter
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.03.2009; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; ATP-binding cassette G2; ATP-Binding Cassette Transporters - metabolism; ATPase; breast cancer resistance protein; enzyme kinetics; Humans; In Vitro Techniques; sulfasalazine; Sulfasalazine - pharmacokinetics; vesicular transport; Vesicular Transport Proteins - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.32.497

The pharmacokinetics of sulfasalazine, an anti-inflammatory drug is influenced by ATP-binding cassette G2 (ABCG2) (breast cancer resistance protein (BCRP), mitoxantrone resistance protein (MXR)) both in vitro and clinically. Due to its low passive permeability, the intracellular concentration of sulfasalazine is dependent on uptake transporters, rendering the characterization of transporter specific interactions in cell based experimental systems difficult. Applying membrane assays a detailed kinetic analysis of sulfasalazine ABCG2 interaction was conducted and Km values of 0.70±0.03 μM and 0.66±0.08 μM were obtained at pH 7.0 and pH 5.5, respectively.