Abstract：
Erdafitinib, a selective and potent oral pan-FGFR inhibitor, is metabolized mainly through CYP2C9 and CYP3A4 enzymes. This phase 1, open-label, single-sequence, drug-drug interaction study evaluated the pharmacokinetics, safety, and tolerability of a single oral dose of erdafitinib alone and when co-administered with steady state oral carbamazepine, a dual inducer of CYP3A4 and CYP2C9, in 13 healthy adult participants (NCT04330248). Compared with erdafitinib administration alone, carbamazepine co-administration decreased total and free maximum plasma concentrations of erdafitinib (Cmax) by 35% (95% CI 30%-39%) and 22% (95% CI 17%-27%), respectively. The areas under the concentration-time curve over the time interval from 0 to 168 hours, to the last quantifiable data point, and to time infinity (AUC168h, AUClast, AUCinf), were markedly decreased for both total erdafitinib (56%-62%) and free erdafitinib (48%-55%). The safety profile of erdafitinib was consistent with previous clinical studies in healthy participants, with no new safety concerns when administered with or without carbamazepine. Co-administration with carbamazepine may reduce the activity of erdafitinib due to reduced exposure. Concomitant use of strong CYP3A4 inducers with erdafitinib should be avoided.
摘要：
Erdafitinib,一种选择性和有效的口服泛FGFR抑制剂，主要通过CYP2C9和CYP3A4酶代谢。第一阶段，开放标签，单序列，药物相互作用研究评估了药代动力学，安全,和单一口服剂量的erdafitinib单独和与稳态口服卡马西平共同给药时的耐受性，CYP3A4和CYP2C9的双重诱导剂，在13名健康成人参与者中（NCT04330248）。与erdafitinib单独给药相比，卡马西平联合给药可使erdafitinib的总和游离最大血浆浓度（Cmax）降低35％（95％CI30％-39％）和22％（95％CI17％-27％），分别。在0至168小时的时间间隔内，浓度-时间曲线下的面积，到最后一个可量化的数据点，和时间无穷大(AUC168h，AUClast,AUCinf),总erdafitinib(56%-62%)和游离erdafitinib(48%-55%)均显著下降。erdafitinib的安全性与以前在健康参与者中的临床研究一致，与卡马西平或不与卡马西平一起使用时，没有新的安全性问题。与卡马西平共同给药可能由于暴露减少而降低erdafitinib的活性。应避免同时使用强CYP3A4诱导剂和erdafitinib。
