A Practice-Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE-01)
JournalClinical and Translational Science
PublisherBlackwell Publishing Ltd
MetadataShow full item record
AbstractLimited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti‐epileptic drug pharmacokinetics (PK). This prospective practice‐based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1‐hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient‐specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12–46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36–73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function. Copyright 2020 The Authors.
SponsorsThis work was supported by the Center for Translational Medicine at the University of Maryland School of Pharmacy.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85082977426&doi=10.1111%2fcts.12782&partnerID=40&md5=de4c0c9e2b9cbbc30849e948777aa089; http://hdl.handle.net/10713/12612
- Optimizing Ceftaroline Dosing in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.
- Authors: Kalaria S, Williford S, Guo D, Shu Y, Medlin C, Li M, Yeung SYA, Ali F, Jean W, Gopalakrishnan M, Heavner M
- Issue date: 2021 Jan 12
- Pharmacokinetics and Pharmacodynamics of Extended-Infusion Cefepime in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Prospective, Open-Label Study.
- Authors: Philpott CD, Droege CA, Droege ME, Healy DP, Courter JD, Ernst NE, Harger NJ, Foertsch MJ, Winter JB, Carter KE, Van Fleet SL, Athota K, Mueller EW
- Issue date: 2019 Nov
- Cefepime and continuous renal replacement therapy (CRRT): in vitro permeability of two CRRT membranes and pharmacokinetics in four critically ill patients.
- Authors: Isla A, Gascón AR, Maynar J, Arzuaga A, Toral D, Pedraz JL
- Issue date: 2005 May
- Population Pharmacokinetics of Cefuroxime in Critically Ill Patients Receiving Continuous Venovenous Hemofiltration With Regional Citrate Anticoagulation and a Phosphate-Containing Replacement Fluid.
- Authors: Janssen PK, Foudraine NA, Burgers DM, Neef K, le Noble JL
- Issue date: 2016 Dec
- Levetiracetam Pharmacokinetics in a Patient with Intracranial Hemorrhage Undergoing Continuous Veno-Venous Hemofiltration.
- Authors: Van Matre ET, Mueller SW, Fish DN, MacLaren R, Cava LF, Neumann RT, Kiser TH
- Issue date: 2017 Apr 27