Epilepsia, 52(2):258–263, 2011 doi: 10.1111/j.1528-1167.2010.02751.x
FULL-LENGTH ORIGINAL RESEARCH
Saliva and serum lacosamide concentrations in patients with epilepsy Clare Greenaway, Neville Ratnaraj, Josemir W. Sander, and Philip N. Patsalos Department of Clinical and Experimental Epilepsy, Pharmacology and Therapeutics Unit, UCL – Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London and Chalfont Centre for Epilepsy, Chalfont St Peter, U.K.
SUMMARY Purpose: Lacosamide is a new antiepileptic drug that has a novel mechanism of action, linear pharmacokinetics, and proven efficacy in the adjunctive treatment of partialonset seizures. We ascertained the relationship between serum and saliva lacosamide concentrations so as to determine whether saliva may be a useful alternative to serum for therapeutic drug monitoring. Methods: Blood samples were obtained from 98 people with intractable epilepsy (51 male; mean age 43 ± 12; range 19–76 years) prescribed lacosamide as adjunctive therapy. For 48 patients, concurrent saliva samples were also collected. Lacosamide concentrations in serum (free and total) and in saliva were determined by high performance liquid chromatography (HPLC). Results: Linear regression analysis showed a good correlation between lacosamide dose and both total
Lacosamide (Vimpat, UCB Pharma, Brussels, Belgium) is a new antiepileptic drug (AED) that was licensed in Europe 2008 and in the United States in 2009. It acts by selectively enhancing the slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing without exhibiting effects on fast inactivation. In addition, lacosamide has been reported to bind to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein that is expressed mainly in the nervous system, and is thought to prevent axonal sprouting of neurons involved in seizure activity (Beyreuther et al., 2007; Doty et al., 2007; Ben-Menachem, 2008). However, this latter mechanism has Accepted August 17, 2010; Early View publication October 13, 2010. Address correspondence to Professor Philip N. Patsalos, Chalfont Centre for Epilepsy, Therapeutic Drug Monitoring Unit, Chesham Lane, Chalfont St Peter, Buckinghamshire SL9 0RJ, United Kingdom. E-mail:
[email protected] Wiley Periodicals, Inc. ª 2010 International League Against Epilepsy
(r2 = 0.825; n = 32) and free (r2 = 0.815; n = 29) serum concentrations, and lacosamide serum total and free concentrations were linearly related (r2 = 0.721; n = 97). There was also a good correlation between saliva lacosamide and both total (r2 = 0.842; n = 49) and free (r2 = 0.828; n = 47) serum lacosamide concentrations. Based on the saliva data, the protein binding of lacosamide in serum is calculated to be 87 ± 4% and is comparable to the value calculated by direct measurement of the free and total lacosamide concentration in serum (91 ± 4%). Discussion: These data support the use of saliva as a viable alternative to serum for monitoring lacosamide therapy in patients with epilepsy. KEY WORDS: Lacosamide, New antiepileptic drug, Therapeutic drug monitoring, Saliva monitoring, Free concentrations.
not been demonstrated conclusively. In randomized controlled trials, lacosamide has been shown to be effective in patients with partial-onset seizures (Ben-Menachem et al., 2007; Cross & Curran, 2009; Halasz et al., 2009). Lacosamide pharmacokinetic characteristics include rapid absorption (Tmax = 1–2 h) after oral ingestion and a bioavailability of 100%, minimal protein binding (
