{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:53:07Z","timestamp":1793533987081,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg\/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight\u2010based loading doses of LEV with respect to established therapeutic target concentrations. Meta\u2010regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight\u2010based dosing) to achieve maximum (C<jats:sub>peak<\/jats:sub>) and 12\u2010h (C<jats:sub>12h<\/jats:sub>) plasma concentrations that exceed 12 mg\/L. The meta\u2010regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg\/kg. Stochastic simulations showed all dosing schemes achieved plasma C<jats:sub>peak<\/jats:sub> &gt;12 mg\/L, but C<jats:sub>12h<\/jats:sub> levels were &lt;12 mg\/L in subjects over 60 kg with a fixed dose \u22642000 mg or in subjects &lt;60 kg with a weight\u2010based dose &lt;30 mg\/kg. Dosages of 40 and 60 mg\/kg provided \u226590% PTAs across all weights. Using a weight\u2010based loading dose of 40 mg\/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed &lt;3000 mg may not achieve the desired concentration before maintenance dosing.<\/jats:p>","DOI":"10.1002\/jcph.2449","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T08:19:14Z","timestamp":1714983554000},"page":"1173-1180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Simulation\u2010Based Assessment of Levetiracetam Concentrations Following Fixed and Weight\u2010Based Loading Doses: A Meta\u2010Regression and Pharmacokinetic Modeling Analysis"],"prefix":"10.1002","volume":"64","author":[{"given":"Anthony","family":"Lau","sequence":"first","affiliation":[{"name":"Emergency Medicine Vancouver General Hospital  Vancouver British Columbia Canada"},{"name":"Faculty of 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