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.