Abstracts

Levetiracetam (LEV) is an antiepileptic drug (AED) with many advantages such as high safety margin, broad spectrum seizure activity, and simple pharmacokinetics. It has nearly 100% bioavailability with peak absorption about 1.3 hours post dose, insignificant protein binding and renal excretion. Current recommendations are to begin LEV at 1000 mg per day in divided dose and increasing 1000 mg/day every two weeks. A recent study starting LEV at 500 mg bid for one day and increasing to 1000 mg bid the next day, found efficacy on the second treatment day correlating with serum concentration. Single doses of LEV in healthy volunteers showed linearity of plasma-time curves over a range of 500 mg -5000 mg. A single 1,000 mg dose achieved peak concentrations of 31 [micro]g/mL, within the steady-state range common for the treatment of epilepsy. We have investigated the effects of a1500 mg loading dose of LEV in epilepsy patients on the epilepsy monitoring unit (EMU), who needed adequate AED therapy prior to discharge, and ICU, where they were undergoing treatment of status epilepticus, for tolerability and efficacy., Patients were given LEV 1500 mg PO or via NG tube with serum concentrations checked two hours after load. Patients were monitored for mental status changes and adverse effects. Additionally gender, weight, height, and creatinine were noted. Post loading EEG was compared to the baseline in all cases., Twelve epilepsy patients, 10 women and 2 men, 18-92 years old (Mean 54 y/o) have been studied. Three were being treated for status epilepticus in the ICU and nine on the EMU for rapid reinstitution of AEDs. Only one patient was previously on LEV. Eleven received oral loading and one ICU patient received loading via NGT. Two hours post loading dose, all patients achived a serum concentration common to the treatment of epilepsy. Serum concentration ranged from 12.8 to 41.2 [micro]g/mL (Mean 31.7; STD 10.4). Weight ranged from 43-146 kg (Mean 84 kg; STD 29). A morbidly obese patient weighing 146 kg (IBW 70 kg) also received LEV via NGT and had a two hour serum concentration of 23 [micro]g/mL. All patients in the EMU were alert before and after load and reported no adverse events. No patients on the EMU had any seizure within 24 hours after load. LEV was well-tolerated in the ICU patients hemodynamically. All were obtunded prior to addition of LEV., Our data suggest that serum concentrations of LEV typical for the treatment of epilepsy may be obtained rapidly and safely after a 1500 mg loading in adults with epilepsy. These data also suggest that oral loading may be used to hasten discharge from the EMU or as adjunctive therapy in status epilepticus though additional study is needed. Loading dose also achieved a therapeutic level in morbid obesity consistent with the high water solubility of the drug.,