Population Pharmacokinetics and Exploratory Exposure-Response Relationships of Diazepam in Children Treated for Status Epilepticus.

Journal Article (Journal Article;Multicenter Study)

Diazepam is labeled for status epilepticus (SE) in children, but there are limited data characterizing its disposition in pediatric patients. We developed a population pharmacokinetic (PK) model of i.v. diazepam in children with SE. We evaluated relationships between PK parameters and both safety and efficacy, and simulated exposures using dosing regimens from the product label and clinical practice. The model was developed using prospective data from a pediatric clinical trial comparing diazepam to lorazepam for treatment of SE. Altogether, 87 patients aged ≥ 3 months to < 18 years contributed 162 diazepam concentrations. Diazepam PKs were well characterized by a two-compartment model scaled by body size. No significant or clinically important relationships were observed between diazepam PKs and safety or efficacy. Simulations demonstrated that, compared with label dosing, the study dose (0.2 mg/kg i.v., maximum 8 mg) resulted in greater frequency in rapidly achieving the target therapeutic range of 200-600 ng/mL.

Full Text

Duke Authors

Cited Authors

  • Ku, LC; Hornik, CP; Beechinor, RJ; Chamberlain, JM; Guptill, JT; Harper, B; Capparelli, EV; Martz, K; Anand, R; Cohen-Wolkowiez, M; Gonzalez, D; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee,

Published Date

  • November 2018

Published In

Volume / Issue

  • 7 / 11

Start / End Page

  • 718 - 727

PubMed ID

  • 30267478

Pubmed Central ID

  • PMC6263663

Electronic International Standard Serial Number (EISSN)

  • 2163-8306

Digital Object Identifier (DOI)

  • 10.1002/psp4.12349


  • eng

Conference Location

  • United States