Clare Greenaway1, Neville Ratnaraj, Josemir W Sander, Philip N Patsalos. 1. 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, UK.
Abstract
PURPOSE: Lacosamide is a new antiepileptic drug that has a novel mechanism of action, linear pharmacokinetics, and proven efficacy in the adjunctive treatment of partial-onset 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 (r(2) = 0.825; n = 32) and free (r(2) = 0.815; n = 29) serum concentrations, and lacosamide serum total and free concentrations were linearly related (r(2) = 0.721; n = 97). There was also a good correlation between saliva lacosamide and both total (r(2) = 0.842; n = 49) and free (r(2) = 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. Wiley Periodicals, Inc.
PURPOSE:Lacosamide is a new antiepileptic drug that has a novel mechanism of action, linear pharmacokinetics, and proven efficacy in the adjunctive treatment of partial-onset 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 (r(2) = 0.825; n = 32) and free (r(2) = 0.815; n = 29) serum concentrations, and lacosamide serum total and free concentrations were linearly related (r(2) = 0.721; n = 97). There was also a good correlation between saliva lacosamide and both total (r(2) = 0.842; n = 49) and free (r(2) = 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. Wiley Periodicals, Inc.
Authors: Patrício Soares-da-Silva; Nuno Pires; Maria João Bonifácio; Ana I Loureiro; Nuno Palma; Lyndon C Wright Journal: Pharmacol Res Perspect Date: 2015-03-30
Authors: Carlos Casas-Fernández; Antonio Martínez-Bermejo; Miguel Rufo-Campos; Patricia Smeyers-Durá; José L Herranz-Fernández; Salvador Ibáñez-Micó; Jaume Campistol-Plana; Helena Alarcón-Martínez; Jaime Campos-Castelló Journal: Drugs R D Date: 2012-12-01