| Title |
Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus
|
|---|---|
| Published in |
Clinical Pharmacokinetics, December 2016
|
| DOI | 10.1007/s40262-016-0486-0 |
| Pubmed ID | |
| Authors |
Daniel Gonzalez, James M. Chamberlain, Jeffrey T. Guptill, Michael Cohen-Wolkowiez, Barrie Harper, Jian Zhao, Edmund V. Capparelli, On behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee |
| Abstract |
Lorazepam is one of the preferred agents used for intravenous treatment of status epilepticus (SE). We combined data from two pediatric clinical trials to characterize the population pharmacokinetics of intravenous lorazepam in infants and children aged 3 months to 17 years with active SE or a history of SE. We developed a population pharmacokinetic model for lorazepam using the NONMEM software. We then assessed exploratory exposure-response relationships using the overall efficacy and safety study endpoints, and performed dosing simulations.Please use the following Running Title: PopPK and PD of Lorazepam In Pediatric Status Epilepticus RESULTS: A total of 145 patients contributed 439 pharmacokinetic samples. The median (range) age and dose were 5.4 years (0.3-17.8) and 0.10 mg/kg (0.02-0.18), respectively. A two-compartment pharmacokinetic model with allometric scaling described the data well. In addition to total body weight (WT), younger age was associated with slightly higher weight-normalized clearance (CL). The following relationships characterized the typical values for the central compartment volume (V1), CL, peripheral compartment volume (V2), and intercompartmental CL (Q), using individual subject WT (kg) and age (years): V1 (L) = 0.879*WT; CL (L/h) = 0.115*(Age/4.7)(0.133)*WT(0.75); V2 (L) = 0.542*V1; Q (L/h) = 1.45*WT(0.75). No pharmacokinetic parameters were associated with clinical outcomes. Simulations suggest uniform pediatric dosing (0.1 mg/kg, to a maximum of 4 mg) can be used to achieve concentrations of 50-100 ng/mL in children with SE, which have been previously associated with effective seizure control. The population pharmacokinetics of lorazepam were successfully described using a sparse sampling approach and a two-compartment model in pediatric patients with active SE. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 55 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 15% |
| Student > Bachelor | 8 | 15% |
| Student > Ph. D. Student | 5 | 9% |
| Other | 4 | 7% |
| Unspecified | 3 | 5% |
| Other | 9 | 16% |
| Unknown | 18 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 24% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 13% |
| Nursing and Health Professions | 7 | 13% |
| Biochemistry, Genetics and Molecular Biology | 3 | 5% |
| Unspecified | 3 | 5% |
| Other | 4 | 7% |
| Unknown | 18 | 33% |
Attention Score in Context
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#14,289,166
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Outputs of similar age from Clinical Pharmacokinetics
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