摘要
目的探讨柔红霉素(DNR)治疗儿童白血病时不同滴注持续时间的药代动力学及其与诱导化疗疗效和心脏毒性反应的关系。方法采用反相高效液相色谱(HPLC)荧光检测法检测61例白血病患儿分别持续滴注柔红霉素30 min、2 h、6 h后的血药浓度。在DNR化疗前后不同阶段监测患儿心电图、心肌酶谱、心彩超等指标。分析DNR三种不同滴注持续时间在患儿体内的药代动力学之间的差异及其对诱导化疗疗效和心脏毒性反应的影响。结果①DNR药代动力学参数t1/2α、Vd、MRT(0-t)和Tmax随着滴注持续时间的延长而延长或升高,AUC(0-t)和Cmax则随着滴注持续时间的延长而降低,三组不同滴注持续时间之间差异有统计学意义(P均<0.05);而CL在三组之间差异无统计学意义(P=0.135)。②DNR不同滴注持续时间对其诱导治疗效应差异无统计学意义(P=0.656)。③DNR滴注持续时间越长,其心脏毒性反应的发生率越低,三组间差异有统计学意义(P=0.035);早期心脏毒性可能增加晚期心脏毒性的发生率。结论DNR不同滴注时间的总疗效可能不变;DNR的心脏毒性与其滴注持续时间可能相关;DNR的早期心脏毒性可作为其晚期心脏毒性的一个危险指标;DNR持续滴注6 h的方式可能较为合理。
Objective To study the relationships between pharmacokinetics,efficacy,heart toxicity of daunorubicin（DNR） administered with different duration.Methods Plasma concentration of DNR in leukemia children after being administered with DNR for 30 minutes,2 hours,6 hours was correspondingly determined by reversed-phase high performance liquid chromatographyand its pharmacokinetics was studied.2.Heart toxicity was monitored by EKG,serum myocardial zymogram,cardiac Doppler ultrasound before and after chemotherapy.3.The difference between DNR pharmacokinetics and the influence on efficacy and toxicity of three administration durations were analyzed.Results 1.There was significant difference in t1/2α,Vd,AUC（0-t）,Tmax,MRT and Cmax among the three different administration durations（P 0.05）,t1/2α,Vd,Tmax and MRT were ascended,but AUC（0-t） and Cmax were reduced along with prolongation of infusion.There was no significant difference in CL（P = 0.135）.2.The efficacy of the three DNR administrations was not significantly different（P = 0.656）.3.The heart toxicity was significantly different（P = 0.035）.The longer DNR infusionis,the lower incidence of heart toxicity.The earlier happened toxicity may enhance the incidence of the later heart toxicity.Conclusions The efficacy of different DNR administration durations might be the same.The incidence of heart toxicity may be related to the duration of infusion.The early toxicity may be a dangerous factor to the later heart toxicity.Continuous infusion of DNR for six hours could be chosen in chemotherapy of leukemia children.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2010年第5期428-432,共5页
Journal of Clinical Pediatrics
