Use of adaptive control with feedback to individualize suramin dosing.

摘要: Suramin is the first putative growth factor inhibitor in clinical trial that has demonstrated antitumor activity. Administration of suramin complicated by a narrow therapeutic index and significant interpatient variability measured pharmacokinetic parameters. Because both response dose-limiting toxicities are related to plasma concentration profiles, individualized dose schedules required for optimal administration compound. In this report, use sampling theory derive sparse data monitoring control strategies with described. A fixed rate continuous infusion schedule was used seven patients, time peak (280–300 μg/ml) ranged from 7.7–21 days (mean, 13.2 days) decline 150 μg/ml 3–22 11 days). An initial population model fit using maximum likelihood algorithm. The mean volume central compartment 4.5 ± 6.7 liters/m2, peripheral 10.6 1.4 distributional half-life 25 5.4 h, elimination 29.7 6.9 h. terminal shorter than previously reported. These parameters were as an iterative 2-stage analysis. resulting 22.3 2.7 h 28.2 5.0 similar, reflecting intensive sampling. analysis then determine times simulate 20 sets protocol designed maintain concentrations defined range. This strategy currently under investigation phase I trials.