Time course of the mean serum asparaginase activity. Data points depicting the mean of the assayed values for samples collected from all patients at each time point are shown; error bars represent SD. The solid curve was generated by fitting the differential equation, dA_s/dt = (I − CL × A_s)/V, to the mean serum asparaginase activity (A_s) versus time (t) data. The value of the drug input function (I) was defined as dose/infusion duration during drug administration and as 0 at all other times. CL (total body clearance) = V_m/(K_m + A_s), where V_m and K_m are the maximum metabolic capacity and Michaelis-Menten constant, respectively; V is the apparent volume of distribution. Estimated values of the iterated parameters were V_m = 124 IU/h per m² and K_m = 0.110 IU/mL, V = 2.79 L/m².