| Title: | Levetiracetam dosing in critically ill patients receiving prolonged intermittent renal replacement therapy |
| Researcher: | Sirichai Chusiri, Jirapat Vamananda, Dhakrit Rungkitwattanakul, Taniya Charoensareerat, Sutthiporn Pattharachayakul, Tatta Sriboonruang, Nattachai Srisawat, Chusak Limotai, Thanompong Sathienluckana & Weerachai Chaijamorn |
| Degree: | Doctor of Pharmacy Program in Pharmaceutical Care |
| Major: | Pharm.D. (Pharm.Care) |
| Faculty of study: | Pharmacy |
| Academic year: | 2568 (2025) |
| Published: | Journal of Critical Care, Volume 91, February 2026, 155246 Click |
Abstract
Objective: Levetiracetam can be significantly removed by prolonged intermittent renal replacement therapy (PIRRT) due to its pharmacokinetic properties. However, dosing guidance for this population is limited. This study aimed to evaluate the probability of target attainment (PTA) for various levetiracetam regimens in critically ill adults receiving PIRRT, using Monte Carlo simulation (MCS).
Methods: A one-compartment model with first-order elimination was developed using published pharmacokinetic data. Simulations incorporated PIRRT modalities (hemodialysis and hemofiltration), with an effluent rate of 18 L/h and varying durations (4, 6, 8, and 10 h). PIRRT was modeled as occurring early (at drug administration) or late (14–20 h post-dose). MCS was conducted in 10,000 virtual patients per regimen over 48 h. The pharmacodynamic target was an area under the concentration-time curve (AUC) of 222–666 mg⋅h/L. Regimens achieving ≥90 % PTA were considered optimal.
Results: Several commonly used regimens failed to achieve adequate PTA. For alternate-day PIRRT with hemofiltration, 500 mg every 12 h or 1000 mg every 24 h were optimal. For alternate-day PIRRT with hemodialysis, 750 mg every 12 h or 1250 mg every 24 h were preferred. For daily PIRRT with either modality, 750 mg every 12 h consistently met PTA targets.
Conclusions: Standard dosing regimens may be inadequate for achieving therapeutic exposure in PIRRT. Optimal dosing varies by PIRRT modality, frequency, and timing. These findings support individualized dosing and highlight the need for clinical validation.
Keywords: Levetiracetam, Prolonged intermittent renal replacement, therapy, Pharmacokinetics, Monte Carlo simulation
ดร. ธนิยา เจริญเสรีรัตน์ และผศ. ดร. ภก.ถนอมพงษ์ เสถียรลัคนา – Dr. Taniya Charoensareerat & Asst. Prof. Dr. Thanompong Sathienluckana. 2568 (2025). Levetiracetam dosing in critically ill patients receiving prolonged intermittent renal replacement therapy. บทความ (Paper). วิทยาศาสตร์สุขภาพ|Health Science. เภสัชศาสตร์ (Pharmacy). เภสัชศาสตรบัณฑิต ภ.บ. (การบริบาลทางเภสัชกรรม) – Pharm.D. (Pharm.Care). หลักสูตรเภสัชศาสตรบัณฑิต สาขาวิชาการบริบาลทางเภสัชกรรม – Doctor of Pharmacy Program in Pharmaceutical Care. Bangkok: Siam University
