Pharmacokinetics of Subcutaneous Levetiracetam in Palliative Care Patients

Abstract

<b><i>Background:</i></b> Seizure control is challenging in the palliative care setting. Subcutaneous (SC) levetiracetam (LEV) is currently an off-label route of administration and effectiveness, tolerability, and pharmacokinetics studies for this route are scarce. <b><i>Objectives:</i></b> This prospective study aimed at evaluating effectiveness and tolerability of SC LEV as well as characterizing its pharmacokinetics. <b><i>Subjects:</i></b> Patients (<i>n</i> = 7) who attended the palliative care clinic between September 2018 and January 2019 with diagnosis of seizures, ≥18 years, and in need of SC route of administration were included in the study. <b><i>Measurements:</i></b> LEV plasma levels were determined using high-performance liquid chromatography and pharmacokinetic analysis were performed using Monolix 2018R2 (France). pH and osmolality of the three SC infusion solutions were also determined. <b><i>Results:</i></b> Seven patients took part in the study. Seizures were controlled in six out of seven patients with doses of 1000 and 3000 mg/day. Adverse effects were mild. pH and osmolality of the SC infusion solutions were within the accepted values reported in the literature. Mean plasma LEV concentrations were 14.4 mg/L (1000 mg/day) and 27.7 mg/L (2000 mg/day). The population clearance (2.5 L/h) and the elimination half-life (10.4 hours) were successfully estimated. <b><i>Conclusions:</i></b> Based on this data, SC LEV was effective and well tolerated. Pharmacokinetic parameters for the SC route were successfully determined.