Title: Effects of CYP3A5 genetic polymorphism on doxorubicin pharmacokinetics and toxicity in acute lymphoblastic leukemia patients
Abstract: Objective To explore the association between genetic polymorphism of CYP3A5 and CYP3 A enzyme activity as well as the pharmacokinetics of doxorubicin. Methods The distribution of genotype of CYP3A5 gene polymorphism in 36 patients with acute lymphoblastic leukemia( ALL) was analyzed with polymerase chain reaction- restriction fragment length polymorphism method and quantitative real- time RT- PCR was used to test the levels of CYP3A5 mRNA. The CYP3 A enzyme activity was detected by midazolam and high performance liquid chromatography was employed to determine the plasma concentration of daunorubicin. Results There were significant differences in CYP3A5 mRNA levels among individual genotype. Patients with CYP3A* 1 gene had a higher activity of CYP3 A enzyme than those with CYP3A5* 3 gene( P 0. 05). There were significant differences in AUC0- 24 hand AUC0- ∞among CYP3A5 genotype in patients with ALL( P 0. 05). No significant difference of t1 /2and Cmaxwas observed. The data of AUC significantly enlarged in patients with cardiac toxicity. Conclusion The expression of CYP3A5 mRNA,activity of CYP3 A enzyme and the plasma concentration of daunorubicin are closely related to CYP3A5 * 3 genetic polymorphism. As a result it has an influence on the ALL patients with different adverse reactions.
Publication Year: 2015
Publication Date: 2015-01-01
Language: en
Type: article
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