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J Pediatr. 2012 Apr;160(4):667-672.e2. doi: 10.1016/j.jpeds.2011.09.048. Epub 2011 Nov 1.

Pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus.

Author information

1
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

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.

PMID:
22050870
PMCID:
PMC3274567
DOI:
10.1016/j.jpeds.2011.09.048
[Indexed for MEDLINE]
Free PMC Article
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