SIMULATION OF DOSING SCENARIOS
Figure 2 illustrates the proportion of patients who achieved our therapeutic target level (12 – 46 mcg/mL) across a range of simulated dosing strategies. At a target level of 12 mcg/mL, 65% of simulated patients who received a dose of 1,000 mg every 12 hours achieved target level in comparison to 53% of simulated patients who received 750 mg and 34% of simulated patients who received 500mg.
Table 4 demonstrates the trough concentration profiles at these various simulated doses. At doses <750 mg the median trough concentration was below the target range, although some patients did achieve therapeutic drug concentrations. The exception were patients who received 250 mg – all of whom had trough concentrations below the target level. Even at higher doses (≥750 mg) some patients still demonstrated trough concentrations below the target level.
Our simulations evaluated levetiracetam concentrations in patients on CRRT receiving a range of doses over a 72-hour period. In Figure 3 , patients received a standard loading dose of 60mg/kg as recommended for treatment of neurological emergencies [39-40] . InFigure 4 , patients received a 750mg loading dose as recommended for patients on IHD. In Figure 5 , patients received no loading dose.
As shown in Figure 3 , the standard loading dose achieved therapeutic drug concentrations within the first 24 hours for almost all simulated patients. Conversely, a significant number of patients who received a reduced (Fig. 4 ) or no loading dose (Fig. 5 ) experienced sub-therapeutic drug concentrations for an extended period – with the majority of patients receiving 250 mg dosing spending the entire 72 hour below target concentration. Only at higher doses (750mg, 1000mg) did median concentrations remain within our target range at 72 hours.