摘要
目的:探讨CYP2C19基因多态性对伏立康唑血浓度、有效性及安全性的影响。方法:根据纳入排除标准,筛选某三甲医院使用伏立康唑的真菌感染患者,采集伏立康唑开始治疗后第4天血液样本,采用HPLC法测定伏立康唑血浓度,采用PCR-芯片杂交法检测患者CYP2C19基因型,考察CYP2C19基因型对患者伏立康唑血浓度的影响,并评估分析临床观察指标、实验室检查,随访跟踪对伏立康唑的安全性和有效性,应用SPSS17.0软件对结果进行统计分析。结果:共纳入42例真菌感染患者,男性12例,女性30例;其中27例快代谢,12例中代谢,3例慢代谢;对目标谷浓度分析发现伏立康唑安全有效浓度范围为1.5～5.0 mg·L^(-1)。结果显示,快、中代谢型C_(min)差异无显著性(P=0.18),C_(min)在慢代谢型与快、中代谢型比较差异有显著性(P=0.003,P=0.04);采用卡方检验对有效率和安全性进行统计分析显示,CYP2C19基因多态性对伏立康唑有效性及安全性的影响差异有显著性(P<0.05)。结论:伏立康唑的血药浓度C_(min)在快、中代谢型患者中无差异,但慢代谢型患者的C_(min)与快、中代谢型患者比较差异较大;且不同CYP2C19基因型对伏立康唑有效性及安全性的影响也有差异。仅根据CYP2C19基因型指导伏立康唑临床用药并不一定达到较好的治疗效果,可联合CYP2C19基因型检测与血药浓度监测来指导伏立康唑的临床个体化给药。
OBJECTIVE To investigate the effect of CYP2 C19 gene polymorphism on the blood concentration,efficacy and safety of voriconazole.METHODS Patients with fungal infection who were treated with voriconazole from a top three hospital were screened according to the inclusion and exclusion criteria.Blood samples were collected after the start of voriconazole treatment and he voriconazole blood concentration was determined by RP-HPLC,and the CYP2 C19 genotype was detected by PCR-chip hybridization.Then the effects of CYP2 C19 genotype on voriconazole blood concentration was investigated.The safety and efficacy of voriconazole were also evaluated according to the clinical observation index,laboratory examination and follow-up.The results were analyzed by SPSS 17.0 software.RESULTS A total of 42 patients with fungal infections were included,including 12 males and 30 females;27 of which had extensive metabolism,12 had intermediate metabolism,and 3 had poor metabolism;The target concentration analysis showed that the effective concentration range are 1.5-5.0 mg·L-1.The results showed that there was no significant difference in Cmin between fast and intermediate metabolizers(P=0.18).There was significant differences of Cmin between poor metabolism and extensive metabolism or intermediate metabolism(P=0.003,P=0.04).The statistical analysis of the efficiency and safety by chi-square test showed that the effect of CYP2 C19 gene polymorphism on the efficacy and safety of voriconazole was statistically significant(P<0.05).CONCLUSION Voriconazole concentrations of Cmin had no differences between extensive metabolism and intermediate metabolism,while poor metabolism patients’Cmin was different from extensive metabolism and intermediate metabolism.and the effect of different CYP2 C19 genotypes on the efficacy and safety of voriconazole is also different.Clinical use of voriconazole guided by CYP2 C19 genotype alone could’t achieve a good therapeutic effect,which should be combined with CYP2 C19 genotype detection and plasma concentration monitoring to guide the clinical individualized dosing of voriconazole.
作者
李宇
张永煌
张蕾
史天陆
樊晖晖
LI Yu;ZHANG Yong-huang;ZHANG Lei;SHI Tian-lu;FAN Hui-hui(Taihe County People’s Hospital,Anhui Fuyang 236600,China;The First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital),Anhui Hefei 230001,China;Binhu Hospital of Hefei,Anhui Hefei 230601,China)
出处
《中国医院药学杂志》
CAS
北大核心
2019年第9期959-962,共4页
Chinese Journal of Hospital Pharmacy
基金
安徽中医药大学研究生科技创新基金项目(编号:201506)
作者简介
李宇,男,硕士,药师,研究方向:临床药学,电话:0558-8660115,E-mail:18119600359@163.com;通讯作者:史天陆,男,在读博士,主任药师,研究方向:临床药学,电话:0551-62283341,E-mail:tianlu828@163.com;通讯作者:樊晖晖,女,本科,主管药师,研究方向:临床药学,电话:0558-8696192,E-mail:490554288@qq.com.
