title: Pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus.
abstract: OBJECTIVE
  To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE.
  
  
  METHODS
  Ten hospitals in the Pediatric Emergency Care Applied Research Network enlisted patients 3 months to 17 years with convulsive SE (status cohort) or for a traditional pharmacokinetics study (elective cohort). Sparse sampling was used for the status cohort, and intensive sampling was used for the elective cohort. Non-compartmental analyses were performed on the elective cohort, and served to nest compartmental population pharmacokinetics analysis for both cohorts.
  
  
  RESULTS
  A total of 48 patients in the status cohort and 15 patients in the elective cohort were enrolled. Median age was 7 years, 2 months. The population pharmacokinetics parameters were: clearance, 1.2 mL/min/kg; half-life, 16.8 hours; and volume of distribution, 1.5 L/kg. On the basis of the pharmacokinetics model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations >30 to 50 ng/mL for 6 to 12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg.
  
  
  CONCLUSIONS
  Lorazepam pharmacokinetics in convulsive SE is similar to earlier pharmacokinetics measured in pediatric patients with cancer, except for longer half-life, and similar to adult pharmacokinetics parameters except for increased clearance.
authors: Division of Emergency Medicine, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC 20010, USA. jchamber@cnmc.org
authors: James M
authors: JM
authors: Chamberlain
authors: Edmund V
authors: EV
authors: Capparelli
authors: Kathleen M
authors: KM
authors: Brown
authors: Cheryl W
authors: CW
authors: Vance
authors: Kathleen
authors: K
authors: Lillis
authors: Prashant
authors: P
authors: Mahajan
authors: Richard
authors: R
authors: Lichenstein
authors: Rachel M
authors: RM
authors: Stanley
authors: Colleen O
authors: CO
authors: Davis
authors: Stephen
authors: S
authors: Gordon
authors: Jill M
authors: JM
authors: Baren
authors: John N
authors: JN
authors: van den Anker
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008140:Lorazepam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013226:Status Epilepticus / Q000378:metabolism*
chemical_list: D008140:Lorazepam