LAUSR

Introduction/Hypothesis: Levetiracetam is frequently utilized as seizure prophylaxis due to its favorable side effect profile compared to other antiepileptic drugs. Levetiracetam is renally eliminated through glomerular filtration and exhibits linear pharmacokinetics. A recent pharmacokinetic study in neurocritical care patients demonstrated that 500 mg every 12 hours of intravenous levetiracetam was not adequate to maintain therapeutic plasma concentrations. Methods: This is a prospective, open label pharmacokinetic and pharmacodynamic evaluation of levetiracetam following SAH in the first 20 days following enrollment. Patients were enrolled if ≥18 years old admitted to the Neurosciences ICU at the University of Colorado Hospital between January 1, 2016 and December 31, 2017 who were initiated on levetiracetam therapy with an admission diagnosis of non-traumatic SAH. Serial plasma concentrations were drawn on day 0, 5, 10, 15, 20 following enrollment in conjunction with a 12-hour timed urine collection. Levetiracetam concentrations were determined utilizing LC-MS/MS. Changes in pharmacokinetic parameters were compared over time. Results: The study enrolled 17 patients with a median age of 60 [51, 65], 76% of patients are female, 88% white, baseline median Hunt and Hess of 3 [2, 4], and median Fisher grade of 4 [3, 4]. The mean levetiracetam clearance (mL/min) is 45.2 ± 49.2, 83.1 ± 91.7, 40.1 ± 23.5, 62.9 ± 29.4, 53.9 ± 27.7 for day 0, 5, 10, 15, and 20 respectively. There is a significant difference in levetiracetam clearance between day 0 vs day 10 mean 28.4 ± 9.3 ml/min (p=0.04). The median half-life (hr) is 8.8 [6.4, 14.3], 6.8 [4.8, 9.3], 6.9 [4.1, 9.8], 6.4 [5.2, 11.0], 6.7 [4.1, 8.7] 7 for day 0, 5, 10, 15, and 20 respectively with no significant differences. The median measured creatinine clearance is 159.2 [86.0, 186.3], 172.4 [136.5, 199.7], 168.8 [123.4, 226.8], 201.1 [160.7, 233.6], 176.4 [139.2, 206.6] day 0, 5, 10, 15, and 20 respectively with significant differences between day 0 vs day 10 (p=0.03). No seizures were noted during the pharmacokinetic evaluation. Conclusions: When compared to baseline there was increased clearance of levetiracetam and measured creatinine clearance throughout the study evaluation with a significant difference seen on day 10 when compared to baseline in patients with SAH.