Pharmacodynamics of high-dose @entity1499 in pediatric XXXX .

@entity1 @entity8 @entity137 @entity391 @entity33 @entity1503 @entity1500 @entity1499
OBJECTIVE: To establish a relationship between the pharmacokinetics of high-dose @entity1499 ( @entity1500 ) and @entity137 in @entity1 of a pediatric oncology department and to reassess @entity1500 concentrations at which the @entity1 would be at high risk for toxic effects. METHODS: This study included 37 @entity1 (227 treatment courses) who received a median dose of 4.87 g/m(2) of @entity1500 in a 4-hour infusion. The population pharmacokinetic parameters of @entity1500 were estimated by parametric (IT2B) and nonparametric methods (NPEM). @entity1503 were evaluated. The relationship between pharmacokinetic parameters and @entity137 was analyzed by logistic regression and multiple linear regression. RESULTS: Equations to predict hematologic and nonhematologic @entity137 were obtained. An increase of 100 micro mol/L in the @entity1500 peak concentration meant a 12% (p = 0.03) higher risk of @entity391 ; a significant delay in @entity1500 elimination implied a 5.76-fold higher risk of @entity33 (p < 0.001). An increase of 1 micro mol/L in the @entity1500 concentration 24 hours after the end of the infusion (Cp(24h)) led to a 43% increase in the risk of @entity8 (p < 0.001). @entity1503 was significantly conditioned by the baseline leukocyte count and Cp(24h) (p < 0.001). CONCLUSIONS: The analysis of high-dose @entity1500 pharmacokinetic/pharmacodynamic relationship to @entity137 has led to equations able to predict @entity137 that are easily applicable to daily practice. Cp(24h) >3.5 micro mol/L was confirmed as an indicator of high risk of @entity137 .
