A Practice-Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE-01).
Clin Transl Sci. 2020 Mar 29;:
Authors: Kalaria SN, Armahizer M, McCarthy P, Badjatia N, Gobburu JV, Gopalakrishnan M
Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on antiepileptic 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 pharmacokinetics 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. Pre-filter, post-filter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1 hour post oral dose, and up to 6 additional time points post-infusion or post oral 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 out of the eleven 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 versus observed total clearance value was approximately 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.
PMID: 32223067 [PubMed – as supplied by publisher]