Targeted Systemic Exposure for Pediatric Cancer Therapy
Pharmacokinetic variability in pediatric patients due to maturational changes in organ function, effects of concomitant disease, and drug toxicity or interactions commonly results in drug clearances that differ by a factor of 4 or 5. This intersubject pharmacokinetic variability has been shown to correlate to an increased likelihood of toxicity in patients with low drug clearances, and therapeutic failure in patients with high drug clearances [1, 2]. Pharmacokinetic and pharmacodynamic modeling strategies have been developed and incorporated into clinical studies intended to define the unique pharmacokinetics of anticancer drugs in pediatric patients, identify clinical correlates (e. g., patient characteristics, laboratory indices of organ function) of pharmacokinetic differences, and adjust dosage regimens to control for pharmacokinetic variability.
KeywordsSystemic Exposure Pharmacokinetic Variability Nonlinear Mixed Effect Model Monte Carlo Simulation Study Structural Model Parameter
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