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.

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.

• 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.)
• Copyright: Copyright © 2012 Mosby, Inc. All rights reserved.

Chemical References

• Lorazepam

Topics

• Adolescent
• Child
• Child, Preschool
• Humans
• Infant
• Infusions, Intravenous
• Lorazepam (administration & dosage, pharmacokinetics)
• Prospective Studies
• Status Epilepticus (metabolism)