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Chamberlain, James M., MD; Capparelli, Edmund V., PharmD; Brown, Kathleen M., MD; Vance, Cheryl W., MD; Lillis, Kathleen, MD; Mahajan, Prashant, MD, MPH, MBA; Lichenstein, Richard, MD; Stanley, Rachel M., MD, MHSA; Davis, Colleen O., MD, MPH, FAAP, FACEP; Gordon, Stephen, MD; Baren, Jill M., MD, MBE, FACEP, FAAP; van den Anker, John N., MD, PhD, FCP, FAAP
The Journal of pediatrics, 04/2012, Letnik: 160, Številka: 4Journal Article
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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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