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. STUDY DESIGN: 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.
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Authors | 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, Pediatric Emergency Care Applied Research Network (PECARN) |
Journal | The Journal of pediatrics
(J Pediatr)
Vol. 160
Issue 4
Pg. 667-672.e2
(Apr 2012)
ISSN: 1097-6833 [Electronic] United States |
PMID | 22050870
(Publication Type: Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright © 2012 Mosby, Inc. All rights reserved. |
Chemical References |
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Topics |
- Adolescent
- Child
- Child, Preschool
- Humans
- Infant
- Infusions, Intravenous
- Lorazepam
(administration & dosage, pharmacokinetics)
- Prospective Studies
- Status Epilepticus
(metabolism)
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