Individualized, pharmacokinetic (PK)-guided hydroxyurea dose selection using sparse sampling. For the determination of an individualized, PK-guided hydroxyurea dose, patients take a single oral 20 mg/kg dose, followed by the collection of blood samples 15, 60, and 180 minutes after the dose. The left side of the figure demonstrates how hydroxyurea concentrations at these timepoints are incorporated into a population PK model to determine the hydroxyurea PK profile and to estimate hydroxyurea exposure, as defined by area under the concentration-time curve (AUC). The right side of the figure illustrates how the individualized PK profile is used to determine the required dose to target an AUC of 115 mg*hour/L, demonstrated to be the mean AUC for a cohort of patients who had achieved the optimal, maximum tolerated dose (MTD). This target dose is then selected as the starting dose.