Abstract
Characterization of human transporter function in vivo requires well‐characterized probe substrates. Fexofenadine (Fex), a safe drug with pharmacokinetics controlled by transporters, may be a useful probe. There is, however, uncertainty regarding the roles of specific transporters in Fex pharmacokinetics. We previously tested a probe drug cocktail in healthy subjects with Fex, buspirone, caffeine, dextromethorphan, and losartan for the measurement of CYP and transporter activities. A Fex‐drug interaction was observed, resulting in a 40% decrease in mean Fex AUC when Fex was given as part of the cocktail. We are now conducting in vitro studies in HeLa cells transfected with human transporters to determine the molecular basis of this interaction. Initial studies with OATP1A2 indicate an interaction between Fex and one or more of the probe drugs. Preliminary results show a Km for Fex of 30 µM, and that losartan appears to be an OATP1A2 substrate. Characterization of the kinetics of these interactions will better define both substrate preferences for OATP1A2 and the role of this transporter in Fex pharmacokinetics. Supported by NIH/NCCAM R21‐AT002907‐03.
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