Büttner Bozena, Knoth Holger, Kramer Michael, Oertel Reinhard, Seeling Andreas, Sockel Katja, von Bonin Malte, Stölzel Friedrich, Alakel Nael, Platzbecker Uwe, Röllig Christoph, Ehninger Gerhard, Bornhäuser Martin, Schetelig Johannes, Middeke Jan Moritz
a Klinikapotheke, Universitätsklinikum Carl Gustav Carus der TU Dresden , Dresden , Germany.
b Universitätsklinikum Carl Gustav Carus der TU Dresden , Medizinische Klinik und Poliklinik I , Dresden , Germany.
Leuk Lymphoma. 2017 Dec;58(12):2865-2874. doi: 10.1080/10428194.2017.1319051. Epub 2017 May 16.
Common side effects of clofarabine (CFB) are liver toxicity, particularly a transient elevation of transaminases and skin toxicity. We studied the correlation of pharmacokinetic (PK) parameters with these toxicities and the efficacy of CFB in patients with relapsed or refractory acute myeloid leukemia. Clofarabine PK parameters showed large inter-individual variability. A higher CFB area under the curve was significantly associated with higher transaminase levels (p = .011 for aspartate aminotransferase (AST), adjusted for age, sex, cumulated CFB dosage, baseline AST, and glomerular filtration rate (GFR)). No significant association could be found between maximum concentration and the liver toxicity parameters. The occurrence of skin toxicity and the response to re-induction chemotherapy evaluated at day 15 were also not associated with PK. In conclusion, a higher individual CFB exposure is associated with increased liver toxicity reflected by elevated liver enzymes, without having an impact on anti-leukemic efficacy.
氯法拉滨（CFB）的常见副作用是肝毒性，尤其是转氨酶短暂升高和皮肤毒性。我们研究了药代动力学（PK）参数与这些毒性以及CFB对复发或难治性急性髓系白血病患者疗效之间的相关性。氯法拉滨的PK参数显示个体间差异很大。曲线下CFB面积较高与转氨酶水平较高显著相关（天冬氨酸转氨酶（AST）的p = 0.011，校正了年龄、性别、CFB累积剂量、基线AST和肾小球滤过率（GFR））。在最大浓度与肝毒性参数之间未发现显著关联。皮肤毒性的发生以及在第15天评估的再诱导化疗反应也与PK无关。总之，个体CFB暴露量较高与肝酶升高所反映的肝毒性增加相关，而对抗白血病疗效无影响。
