Population Pharmacokinetics and Exploratory Exposure‐Response Relationships of Diazepam in Children Treated for Status Epilepticus
Year: 2018
Type: article
Abstract: 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.
DOI: 10.1002/psp4.12349
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,140
Funders: Children's Hospital of Philadelphia, University of Pennsylvania, University of Louisville, Pennsylvania State University, National Institutes of Health, University of North Carolina at Chapel Hill, University of California, San Diego, Penn State College of Medicine, National Institute of General Medical Sciences, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Duke Clinical Research Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2893705759