Plasma concentrations simulated with the final model to reach C(30 min’) between 10 and 12 mg/L. Simulations for 30 min infusion time. (a) Plasma-concentration time curves. Grey, 95% CI of the simulated concentrations (from 100 simulations per subject, i.e., 10,900 simulations in total). Red, median C(t) at each time point. Blue horizontal lines show recommended maximal trough (1 mg/L), and maximal C(30 min’) level for long-duration treatment (12 mg/L). Horizontal dotted and broken lines, 95% CI of the simulated C(30 min’) and maximal levels (at infusion stop), respectively. Vertical dotted red line, time point for C(30 min’). (b) Distribution of the simulated C(30 min’). Vertical blue line, 12 mg/L. Vertical black broken lines, 95% CI of the simulated C(30 min’). (c) Distribution of the simulated C(24 h’). Vertical blue line, 1 mg/L. Vertical black broken lines, 95% and 99% upper CI of the simulated C(24 h’). The 95% and 99% CI values for the simulated C(30 min’) and C(24 h’) are provided in panel (c).