Dasatinib (DAS) is a narrow therapeutic index drug and novel oral multitarget inhibitor of tyrosine kinase and approved for the first-line therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome (Ph + ) acute lymphoblastic leukemia (ALL). DAS, a known potent substrate of cytochrome (CYP) 3A, P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) and is subject to auto-induction. The dietary supplementation of sinapic acid (SA) or concomitant use of SA containing herbs/foods may alter the pharmacokinetics as well as pharmacodynamics of DAS, that may probably lead to potential interactions. Protein expression in rat hepatic and intestinal tissues, as well as the in vivo pharmacokinetics of DAS and the roles of CYP3 A2 and drug transporters Pgp-MDR1 and BCPR/ABCG2, suggested a likely interaction mechanism. The single dose of DAS (25 mg/kg) was given orally to rats with or without SA pretreatment (20 mg/kg p.o. per day for 7 days, n = 6). The plasma concentration of DAS was estimated by using Ultra-High-Performance Liquid Chromatography Mass spectrometry (UHPLC-MS/MS). The in vivo pharmacokinetics and protein expression study demonstrate that SA pretreatment has potential to alter the DAS pharmacokinetics. The increase in C_max, AUC and AUMC proposes increase in bioavailability and rate of absorption via modulation of CYP3 A2, PgP-MDR1 and BCPR/ABCG2 protein expression. Thus, the concomitant use of SA alone or with DAS may cause serious life-threatening drug interactions.

达沙替尼（DAS）是一种窄治疗指数药物和新型口服多靶点酪氨酸激酶抑制剂，被批准用于慢性粒细胞白血病（CML）和费城染色体（Ph+）急性淋巴细胞白血病（ALL）的一线治疗。DAS 是细胞色素 (CYP) 3A、P-糖蛋白 (Pgp) 和乳腺癌抗性蛋白 (BCRP) 的已知有效底物，可进行自诱导。饮食中补充芥子酸 (SA) 或同时使用含有芥子酸的草药/食物可能会改变 DAS 的药代动力学和药效学，这可能会导致潜在的相互作用。大鼠肝和肠组织中的蛋白质表达，以及DAS 的体内药代动力学以及 CYP3 A2 和药物转运蛋白 Pgp-MDR1 和 BCPR/ABCG2 的作用，表明可能存在相互作用机制。给有或没有SA预处理的大鼠口服单剂量DAS（25 mg/kg）（每天口服20 mg/kg，持续7天，n = 6）。使用超高效液相色谱质谱法 (UHPLC-MS/MS) 估算 DAS 的血浆浓度。体内药代动力学和蛋白质表达研究表明，SA 预处理有可能改变 DAS 药代动力学。C _max 、AUC 和 AUMC的增加表明通过调节 CYP3 A2、PgP-MDR1 和 BCPR/ABCG2 蛋白表达来增加生物利用度和吸收率。因此，单独使用 SA 或与 DAS 联合使用可能会导致严重危及生命的药物相互作用。