The relationship between asparaginase enzymatic activity of the pegaspargase and its substrate (asparagine). The results are shown as a sigmoid pharmacodynamic relationship between the population mean of deaminated asparagine levels expressed as a percentage of pretreatment controls versus log10 of asparaginase enzymatic activity. The sigmoid relationship is of the third order of regression, as it is the upper portion of the sigmoid fit according to the Michelis-Menten reaction. Of note is that the time does not appear in the figure since it is embedded in the PPK of asparaginase enzymatic activity, which was obtained from Figure 2. Minimal enzymatic activity of 0.2 IU/mL was needed for optimal asparagine deamination of 90% compared with the baseline. Horizontal line indicates 90% of asparagine depletion below pretreatment levels; vertical line, 0.2 IU/mL of asparaginase activity; and ASN, asparagine.
