Population Pharmacokinetics and Exploratory Exposure‐Response Relationships of Diazepam in Children Treated for Status Epilepticus. (28th September 2018)

• Record Type: Journal Article
• Authors: Ku, Lawrence C.; Hornik, Christoph P.; Beechinor, Ryan J.; Chamberlain, James M.; Guptill, Jeffrey T.; Harper, Barrie; Capparelli, Edmund V.; Martz, Karen; Anand, Ravinder; Cohen‐Wolkowiez, Michael; Gonzalez, Daniel
• Other Names: Furda Gary investigator.; Benjamin Danny investigator.; Kearns Gregory L. investigator.; Paul Ian M. investigator.; Sullivan Jan investigator.; Hornik Christoph P. investigator.; Wade Kelly investigator.; Siegel David investigator.; Taylor‐Zapata Perdita investigator.; Zajicek Anne investigator.; Ren Zhaoxia investigator.; Tsilou Ekaterini investigator.; Pagan Alice investigator.; Simone Gina investigator.; Ku Lawrence investigator.; Mills Mary investigator.; Watt Kevin investigator.
• Is Part Of: CPT: pharmacometrics & systems pharmacology. Volume 7:Number 11(2018)
• Page Start: 718
• Page End: 727
• Publication Date: 2018-09-28
• Subjects: Pharmacokinetics -- Periodicals; Pharmacology -- Periodicals; Pharmacokinetics; Periodicals; 615.05
• DOI: 10.1002/psp4.12349
• Languages: English
• ISSNs: 2163-8306

Abstract

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.