| Objective: Monitoring daunorubicin(DNR) concentration in plasma of children with acute leukemia after administration,Study daunorubicin Pharmacokinetics of children with acute leukemia and relationships between Pharmacokinetics and efficacy and toxicity.Method: (1) Daunorubicin concentration in plasma of children with acute leukemia was determinated by reversed—phase high performance liquid chromatography (HPLC). (2) Plasma was sampled frequently from the start of the infusion at 0.25h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h. DNR Pharmacokinetics was studied by determinating the concentrations in plasm in 24h. (3) Efficacy and toxicity were been monitoring in each period after chemotherapy. Laboratory studies included examination of bone marrow, white blood cell count, the fuction of heart (electrocardiogram, myocardium enzymogram ,cTnT,cTnI), the fuction of liver and kidney. (4) The relationships between Pharmacokinetics and gender, age, weight, efficacy and toxicity were analysised.Result: (1) The chromatography was good and not interfered by the components of the plasma in determinating DNR concentration in plasma by HPLC, the lowest concentration of quantification for DNR was 1.0ng/ml in plasma.A linear calibration curve was obtained from 5.0 ng/ml up to 1500ng/m1.The recovery was 96.31～105.40%. The intraday variation was 1.36～3.24 % and the interday variation was 1.53～4.32%. (2): Daunorubicin Pharmacokinetics: 1) Result showed that the concentration increased quickly after infusion and also decreased quickly to a very low level from the end of 2 hours'infusion in 20 patients. Tmax was 1～3 hours , the mean Tmax was 1.45 hours. 2) DNR was eliminated from plasma in a two-compartment manner, t1/2α:0.59±0.41h, t1/2β:37.97±28.77h, CL:72.28±37.92L/h/m2, AUC:379.10±249.78ug/L·h, Tmax:1.45±0.72h,Cmax:73.40±33.57ug/L. 3) There was a large individual variety of pharmacokinetic parameters of DNR .The difference of CL was 9-fold, AUC was 8-fold,Cmax was 5-fold. (3) The relationships between Pharmacokinetics and gender, age, weight. 1)The CL in malepatients was 57.99L/h/m2, 93.71 L/h/m2 in female, The CL in male patients wassignificantly lower than female patients ( P﹤0.05 ) . Tmax of male patients wasmoderate quicker than female patients(P=0.065). 2) The correlation between weight and Tmax was significant.(r=0.447,P﹤0.05). There was moderate correlation between age. and Tmax ( r=-0.421,P=0.064). There was moderate correlation between age and Cmax (r=0.403,P=0.078). (4). AUC in group of having cardiotoxicity was higher than group of having no cardiotoxicity, the difference was significant ( P﹤0.05 ). (5) The correlations between AUC and concentration at 4h and concentration at 6h plasma samples were the best( r=0.953, P﹤0.05; r=0.976, P﹤0.05, respectively).Conclusion: (1) This method has been verified to be accurate and sensitive. It is suitable to determinate the concentration of DNR in plasma. (2) There is a large individual variety of pharmacokinetic parameters of DNR in children. It predicts large individual variety of efficacy and toxicity. It is important to therapeutic drug monitoring. (3) Male patients had a higher bioavailability and lower metabolism. It indicates that male patients are easy to occur toxicity and need lower dose. Age and weight have influence on Cmax and Tmax. It indicates that older children are easy to occur toxicity and need lower dose . (4) Cardiotoxicity of DNR is dependent on AUC. It means patients with high AUC probably need lower dose. (5) The mean Tmax is1.45h. The correlations between AUC and the concentration at 4h and 6h plasma samples are the best. It is suggested to monitoring concentration at 1.45h , 4h and 6h from the start of 2 hours'infusion.
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