Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita University Hospital, Akita, Japan.
Pharmacology. 2011;87(5-6):241-8. doi: 10.1159/000324900. Epub 2011 Apr 6.
Imatinib is approved as a first-line treatment for Philadelphia chromosome-positive chronic myeloid leukemia (CML). Because of the variability in imatinib exposure among patients, therapeutic drug monitoring to maintain a plasma threshold level of about 1,000 ng/ml would be beneficial during imatinib therapy. Imatinib pharmacokinetics are influenced by body weight, comedication and pharmacogenetic factors, and the drug is excreted into the bile by the breast cancer resistance protein (ABCG2 gene). To attain the plasma threshold of approximately 1,000 ng/ml, the daily dose for patients with the ABCG2 421C/C genotype should be 400 mg; for patients with the 421C/A or 421A/A genotype, the dose should be 300 mg. Knowledge of the ABCG2 421 genotype could be useful when making dosing decisions aimed at achieving the optimal imatinib exposure. A therapeutic drug monitoring service should be routinely provided to CML patients taking imatinib. For CML patients who have an imatinib trough level of 1,000 ng/ml but lack a sufficient clinical response, switching to another tyrosine kinase inhibitor is recommended.
伊马替尼被批准作为费城染色体阳性慢性髓性白血病（CML）的一线治疗药物。由于患者之间伊马替尼暴露的可变性，在伊马替尼治疗期间，维持血浆阈值水平约 1000ng/ml 的治疗药物监测将是有益的。伊马替尼的药代动力学受体重、合并用药和遗传药理学因素的影响，药物通过乳腺癌耐药蛋白（ABCG2 基因）被排入胆汁。为了达到约 1000ng/ml 的血浆阈值，ABCG2 421C/C 基因型患者的每日剂量应为 400mg；对于 421C/A 或 421A/A 基因型的患者，剂量应为 300mg。在制定旨在实现最佳伊马替尼暴露的剂量决策时，了解 ABCG2 421 基因型可能会很有用。应常规为接受伊马替尼治疗的 CML 患者提供治疗药物监测服务。对于伊马替尼谷浓度为 1000ng/ml 但缺乏足够临床反应的 CML 患者，建议换用另一种酪氨酸激酶抑制剂。
