• James M Chamberlain, Edmund V Capparelli, Kathleen M Brown, Cheryl W Vance, Kathleen Lillis, Prashant Mahajan, Richard Lichenstein, Rachel M Stanley, Colleen O Davis, Stephen Gordon, Jill M Baren, John N van den Anker, and Pediatric Emergency Care Applied Research Network (PECARN).
• 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
• J. Pediatr. 2012 Apr 1; 160 (4): 667-672.e2.

ObjectiveTo 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.Study DesignTen 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.ResultsA 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.ConclusionsLorazepam 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.Copyright © 2012 Mosby, Inc. All rights reserved.

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