Change Of Daunorubicin Pharmacokinetics Used In Three Ways Of Children With Acute Leukemia And Influence Of Daunorubicin Administration On Efficacy And Toxicity

Objective:To monitor daunorubicin(DNR) concentration in plasma of children with acute leukemia after three administration, to study the relationships daunorubicin Pharmacokinetics used in different ways of children with acute leukemia and relationships between Pharmacokinetics and efficacy and toxicity.Method:1. Daunorubicin concentration in plasma of children with various infusion was determinated by reversed-phase and daunorubicin pharmacokinetics was studied by reversed-phase high performance liquid chromatography (HPLC).2. Efficacy and toxicity were been monitoring in each period before and after chemotherapy. Laboratory studies included examination of bone marrow, white blood cell count, the fuction of heart (electrocardiogram, myocardium enzymogram), the fuction of liver and kidney.3. The difference among daunorubicin Pharmacokinetics and the influence to efficacy and toxicity of daunorubicin used in three ways were analysised.Result:1. Daunorubicin Pharmacokinetics of children with acute leukemia:①. there was a large individual variety of pharmacokinetic parameters of DNR .②. The relationships between Pharmacokinetics and various administration of daunorubicin: it was showed significant difference to t1/2α,Vd,AUC(0-t),Tmax,MRT and Cmax among various administration of daunorubicin(P﹤0.05), t1/2α,Vd,Tmax and MRT were ascended , but AUC(0-t) and Cmax were reduced along with prolongation of infusion. It was not showed significant difference to CL(P=0.244).2. The relationships between efficacy,toxicity and various administration:①.The efficacy of daunorubicin used in different ways was not significantly different (P= 0.656).②. The toxicity of daunorubicin used in different ways to the heart was significantly different(P=0.035). And with prolongation of infusion, the incidence of the toxicity to the heart was lower. The earier toxicity may enhance the incidence of the later toxicity to the heart.③. The toxicity of daunorubicin used in different ways to the liver was not significantly different(P=0.815).④.The toxicity of DNR used in different ways to the liver was not significantly different(P>0.05).Conclusion:1. AUC(0-t) and Cmax were reduced and sustaining time of effective concentration was longer along with prolongation of infusion. The pharmacological effect may be same.2. The incidence of the toxicity to the heart was interrelated to time of infusion.3. The earier toxicity may be a dangerous factor to the later toxicity to the heart.4. The way used in 6h of infusion may be reasonable in children.