Quantitative prediction of drug interactions based on the inhibition of hepatic uptake transporters

基于基于生理学的药代动力学模型，分析了涉及肝脏摄取转运蛋白的药物相互作用。例如，伊曲康唑和吉非罗齐联合给药导致的瑞格列奈浓度增加可通过瑞格列奈的肝脏摄取和代谢抑制进行定量解释。应用本模型分析定量预测涉及肝摄取转运蛋白的药物相互作用，预计将有助于提高药物开发效率和避免毒性相互作用。

Drug-drug interactions involving the hepatic uptake transporters were analyzed based on a physiologically based pharmacokinetic model. As an example, the repaglinide concentration increase by co-administration of itraconazole and gemfibrozil was quantitatively explained by the inhibition of both hepatic uptake and metabolism of repaglinide. Application of the present model analysis to quantitative predictions of drug interactions involving hepatic uptake transporters is expected to facilitate the increased efficiency in drug development and avoidance of toxic interactions.