title: Levetiracetam compared to valproic acid: plasma concentration levels, adverse effects and interactions in aneurysmal subarachnoid hemorrhage.
abstract: OBJECTIVE
  Both valproic acid and levetiracetam are anti-epileptic drugs, often used either alone or in combination. The present study compares valproate (VPA) with levetiracetam (LEV) as an intravenous (i.v.) anticonvulsant treatment in intensive care patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of seizures.
  
  
  METHODS
  A prospective, single-center patient registry of 35 intensive care unit (ICU) patients with onset seizure and/or high risk of seizures underwent an anticonvulsive, first-line single treatment regimen either with VPA or LEV. Plasma concentrations (pc), interactions between drugs in the ICU context, adverse effects and seizure occurrences were observed and recorded.
  
  
  RESULTS
  A significant decrease in the pc in patients treated with LEV was observed after changing from intravenous (160±51μmol/l) to enteral liquid application (113±58μmol/l), corresponding to a 70.3% bioavailability for enteral liquid applications. The pc in VPA patients decreased significantly, from (491±138μmol/l) to (141±50μmol/l), after adding meropenem to the therapy (p<0.05). Three epileptic seizures occurred during anticonvulsive therapy in the LEV group, and two in the VPA group, including one non-convulsive status epilepticus (NCSE).
  
  
  CONCLUSIONS
  Though this finding needs further verification, the enteral liquid application of levetiracetam seems to be associated with lower bioavailability than the common oral application of levetiracetam. The use of the antibiotic drug meropenem together with valproic acid leads to lower pc levels in patients treated with of valproic acid. For clinical practice, this indicates the need to monitor the levels of valproic acid in combination with meropenem.
authors.affiliation: Neurocritical Care Unit, Department of Neurosurgery, University Hospital Zurich, Switzerland. s.mink-neuro@bluewin.ch
authors.forename: S
authors.initials: S
authors.lastname: Mink
authors.forename: C
authors.initials: C
authors.lastname: Muroi
authors.forename: M
authors.initials: M
authors.lastname: Seule
authors.forename: M
authors.initials: M
authors.lastname: Bjeljac
authors.forename: E
authors.initials: E
authors.lastname: Keller
mesh_terms: D000284:Administration, Oral; D000368:Aged; D017542:Aneurysm, Ruptured / Q000150:complications; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001682:Biological Availability; D002545:Brain Ischemia / Q000150:complications; D003422:Critical Care; D004347:Drug Interactions; D004750:Enteral Nutrition; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D000077287:Levetiracetam; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D011446:Prospective Studies; D012640:Seizures / Q000517:prevention & control; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*; D013845:Thienamycins / Q000009:adverse effects; D014635:Valproic Acid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D013845:Thienamycins; D000077287:Levetiracetam; D014635:Valproic Acid; D000077731:Meropenem; D010889:Piracetam