• Chiat Ling Jasmine Ong, Pheck Suan June Goh, Miqi Mavis Teo, Tze Peng Lim, Kau Kiat Kelvin Goh, Xiu Yun Ang, Li Juan Kellyn Lim, Nur Hidayah Binte Jamaludin, Beng Ti Ang, and Lay Hoon Andrea Kwa.
• Department of Pharmacy, Singapore General Hospital, Singapore, Singapore. Electronic address: jasmine.ong.c.l@sgh.com.sg.
• J Crit Care. 2021 Aug 1; 64: 255-261.

Background/ObjectivesThe pharmacokinetics (PK) of drugs is dramatically altered in critical illness. Augmented renal clearance (ARC), a phenomenon characterized by creatinine clearance (CrCl) greater than 130 ml/min/1.73m2, is commonly described in critically ill patients. Levetiracetam, an antiepileptic drug commonly prescribed for seizure prophylaxis in the neurosurgical ICU, undergoes predominant elimination via the kidneys. Hence, we hypothesize that current dosing practice of intravenous (IV) levetiracetam 500 mg twice daily is inadequate for critically ill patients due to enhanced drug elimination. The objectives of our study were to describe the population PK of levetiractam using a nonparametric approach to design an optimal dosing regimen for critically ill neurosurgical patients.MethodsThis was a prospective, observational, population PK study. Serial blood samples were obtained from neurosurgical ICU patients who received at least one dose of IV levetiracetam. We used uHPLC to analyze these samples and Pmetrics™ software to perform PK analysis.ResultsTwenty subjects were included, with a median age of 54 years and CrCl of 104 ml/min. A two-compartmental model with linear elimination adequately described the profile of levetiracetam. Mean clearance (CL) was 3.55 L/h and volume of distribution (V) was 18.8 L. No covariates were included in the final model. Monte Carlo simulations showed a low probability of target attainment (PTA, trough at steady state of ≥6 mg/L) with a standard dose of 500 mg twice daily. A dose of at least 1000 mg twice daily was required to achieve 80% PTA. Two subjects, both with subtherapeutic trough levels, developed early onset seizures.ConclusionOur study examined the population PK of levetiracetam in a critically ill neurosurgical population. We found that this population displayed higher clearance and required higher doses to achieve target levels.Copyright © 2021 Elsevier Inc. All rights reserved.

12 keywords...

hide…