The Pharmacokinetics of Levetiracetam in Critically Ill Adult Patients: An Intensive Care Unit Clinical Study
Source abstract
Abstract
The aim of this study was to investigate levetiracetam pharmacokinetics in critically ill adult intensive care patients and to identify pathophysiological factors affecting its kinetics. Fourteen critically ill patients in an intensive care unit were enrolled in the study and received intravenous levetiracetam. Blood samples were collected at specific time points to determine the levetiracetam pharmacokinetics. Patient characteristics such as renal function, demographics, disease severity, organ dysfunction, and biochemical laboratory tests were evaluated for their influence on the kinetics of levetiracetam. Estimated glomerular filtration rate (eGFR) had a statistically significant (p = 0.001) effect on levetiracetam clearance. None of the other patient characteristics had a statistically significant effect on the pharmacokinetics. Simulations of dosing regimens revealed that even typically administered doses of levetiracetam may result in significantly increased concentrations and risk of drug toxicity in patients with impaired renal function. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score differed significantly among the three groups with different epileptic activity (p = 0.034). The same groups also differed in terms of renal function (p = 0.031). Renal dysfunction should be considered when designing levetiracetam dosage. Patients with a low APACHE II score had the lowest risk of experiencing epileptic seizures.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Epilepsy research and treatment · Pharmacological Effects and Toxicity Studies · Antibiotics Pharmacokinetics and Efficacy
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece
ICU, Latsio Burn Center, Thriassio General Hospital of Elefsina, 19600 Attica, Greece
Department of Mathematics, University of Crete, Heraklion, 70013 Crete, Greece
References (46)
Show source-provided references
1. UpToDate® (2021, October 26). Levetiracetam: Drug Information. Available online: https://www.uptodate.com/contents/levetiracetam-druginformation?topicRef=128153&source=see_link.
2. Levetiracetam in the treatment of status epilepticus in adults: A study of 13 episodes10.1159/000087385 ↗
3. The use of levetiracetam in refractory status epilepticus10.1016/j.seizure.2005.12.003 ↗
4. Administration of Levetiracetam in Traumatic Brain Injury: Is it Warranted?
5. The Effect of Keppra Prophylaxis on the Incidence of Early Onset, Post-traumatic Brain Injury Seizures
6. Levetiracetam Prophylaxis for Post-traumatic Brain Injury Seizures is Ineffective: A Propensity Score Analysis10.1007/s00268-016-3606-y ↗
7. Population Pharmacokinetics of Levetiracetam in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage Exhibiting Augmented Renal Clearance10.1007/s40262-020-00979-8 ↗
8. Clinical pharmacology and pharmacokinetics of levetiracetam10.3389/fneur.2013.00192 ↗
9. Levetiracetam intravenous infusion: A randomized, placebo-controlled safety and pharmacokinetic study10.1111/j.1528-1167.2006.00586.x ↗
10. Clinical Pharmacokinetics of Levetiracetam10.2165/00003088-200443110-00002 ↗
11. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration10.1007/s13318-014-0227-4 ↗
12. The safety of levetiracetam10.1517/14740338.6.3.241 ↗
13. Review on the relevance of therapeutic drug monitoring of levetiracetam10.1016/j.seizure.2018.09.004 ↗
14. Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies10.1111/j.1528-1167.2008.01561.x ↗
15. An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs10.1007/s40268-016-0148-6 ↗
16. Levetiracetam clinical pharmacokinetics in elderly and very elderly patients with epilepsy10.1016/j.eplepsyres.2011.08.020 ↗
17. Pharmacokinetics of levetiracetam in infants and young children with epilepsy10.1111/j.1528-1167.2007.01090.x ↗
18. Prospective assessment of levetiracetam pharmacokinetics during dose escalation in 4- to 12-year-old children with partial-onset seizures on concomitant carbamazepine or valproate10.1016/j.eplepsyres.2006.12.005 ↗
19. Levetiracetam Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemofiltration and Venoarterial Extracorporeal Membrane Oxygenation10.1002/phar.1615 ↗
20. Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction10.1007/s12028-016-0242-1 ↗
21. Augmented renal clearance of vancomycin and levetiracetam in a traumatic brain injury patient10.1007/s12028-013-9837-y ↗
22. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 201710.1055/s-0037-1600991 ↗
23. Pharmacokinetic and pharmacodynamic modeling of levetiracetam: Investigation of factors affecting the clinical outcome10.1080/00498254.2020.1746981 ↗
24. (2016). Keppra UCB Pharma Limited, Summary of Product Characteristics, Keppra SmPC, UCB Pharma S.A.. Available online: https://www.medicines.org.uk/emc/product/2293/smpc#gref.
25. Population Pharmacokinetics and Dosing Recommendations of Levetiracetam in Adult and Elderly Patients with Epilepsy10.1016/j.xphs.2020.02.018 ↗
26. Population pharmacokinetics of levetiracetam in Japanese and Western adults10.2165/00003088-200746060-00004 ↗
27. Retrospective population pharmacokinetic analysis of levetiracetam in children and adolescents with epilepsy: Dosing recommendations10.2165/00003088-200847050-00004 ↗
28. Steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients10.1592/phco.31.10.934 ↗
29. Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus10.1111/j.1528-1167.2008.01889.x ↗
30. Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy10.1001/archneurol.2012.445 ↗
31. Therapeutic Drug Monitoring of Levetiracetam in Select Populations10.18433/jpps30081 ↗
32. (2022, January 17). ICH Harmonized Tripartite Guideline for Good Clinical Practice, E6(R2). Available online: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-6-r2-guideline-good-clinical-practice-step-5_en.pdf.
33. ICH Topic E9 Statistical Principles for Clinical Trials (2022, January 17). Note for Guidance on Statistical Principles for Clinical Trials (CPMP/ICH/363/96). Available online: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-9-statistical-principles-clinical-trials-step-5_en.pdf.
34. (2022, January 17). Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the Protection of Natural Persons with Regard to the Processing of Personal Data and on the Free Movement of Such Data, and Repealing Directive 95/46/EC (General Data Protection Regulation. Available online: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32016R0679.
35. (2022, January 17). Directive (EU) 2016/680 of the European Parliament and of the Council of 27 April 2016 on the Protection of Natural Persons with Regard to the Processing of Personal Data by Competent Authorities for the Purposes of the Prevention, Investigation, Detection or Prosecution of Criminal Offences or the Execution of Criminal Penalties, and on the Free Movement of Such Data, and Repealing Council Framework Decision 2008/977/JHA. Available online: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32016R0679.
36. Scoring Systems for the Patients of Intensive Care Unit10.4266/acc.2018.00185 ↗
37. Fleisher, G., Ludwig, S., Bachur, R., Gorelick, M., and Shaw, K. (2010). Textbook of Pediatric Emergency Medicine (Textbook of Pediatric Medicine (Fleisher)), Lippincott Williams & Wilkins. [6th ed.].
38. Comparison of prediction equations to estimate glomerular filtration rate in Chinese patients with chronic kidney disease10.1111/j.1445-5994.2010.02398.x ↗
39. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), A new equation to estimate glomerular filtration rate10.7326/0003-4819-150-9-200905050-00006 ↗
40. GFR estimation: From physiology to public health10.1053/j.ajkd.2013.12.006 ↗
41. Population Pharmacokinetic Modeling of Levetiracetam in Pediatric and Adult Patients With Epilepsy by Using Routinely Monitored Data10.1097/FTD.0000000000000291 ↗
42. Population pharmacokinetics and dose-response relationship of levetiracetam in adult patients with epilepsy10.1016/j.eplepsyres.2017.02.011 ↗
43. Population pharmacokinetics of levetiracetam and dosing recommendation in children with epilepsy10.1111/j.1528-1167.2008.01974.x ↗
44. Himmelfarb, J., and Alp Ikizler, T. (2019). Chronic Kidney Disease, Dialysis, and Transplantation: A Companion to Brenner and Rector’s the Kidney, Elsevier. [4th ed.].
45. Population Pharmacokinetics of Levetiracetam: A Systematic Review10.1007/s40262-020-00963-2 ↗
46. Methaneethorn, J., and Leelakanok, N. (Curr. Clin. Pharmacol., 2021). Population Pharmacokinetics of Levetiracetam: A Systematic Review, Curr. Clin. Pharmacol., ahead of print.