Therapeutic drug management of tyrosine kinase inhibitor

由于患者之间酪氨酸激酶抑制剂（TKI）暴露的差异性，在TKI治疗期间进行治疗药物监测（TDM）以维持一定的固定血浆阈值水平将是有益的。应定期向服用TKI的患者提供TDM服务。在尼洛替尼治疗前，可通过前瞻性UGT 1A 1基因分型确定高胆红素血症风险增加的患者。对于CML患者，尼洛替尼的血药谷浓度阈值的有效性应设定在800 ng/mL以上。达沙替尼的疗效和安全性与暴露量（AUC）相关。与没有突变的患者相比，在T315 I患者中检测到较低的达沙替尼暴露。 这些数据表明，充分暴露于达沙替尼可通过充分抑制BCR-ABL激酶来抑制克隆进化。CML患者达沙替尼的血药谷浓度不应超过2.5 ng/mL。

Because of the variability in tyrosine kinase inhibitor(TKI) exposure among patients, therapeutic drug monitoring (TDM) to maintain a certain fixed plasma threshold level would be beneficial during TKI therapy. TDM service should be routinely provided to patients taking TKI. Patients at increased hyperbilirubinemia risk could be identified by prospective UGT1A1 genotyping prior to nilotinib therapy. The efficacy of the threshold plasma trough concentration of nilotinib should be set above 800 ng/mL for CML patients. Dasatinib efficacy and safety were associared with exposure (AUC). A lower dasatinib exposure was detected among patients with T315I compared to those without the mutation. These data suggest that sufficient exposure of dasatinib may prohibit clonal evolution by adequately inhibiting BCR-ABL kinase. And plasma trough concentration of dasatinib should not exceed 2.5 ng/mL in CML patients.