Saliva and Serum Levetiracetam Concentrations in Patients With Epilepsy

Abstract

Although antiepileptic drug (AED) monitoring in saliva may have some clinical applicability, it has not yet come into routine use. The correlation between levetiracetam (LEV) saliva and serum concentrations also remains unclear. To confirm LEV saliva assay as a useful, noninvasive alternative to serum measurement, we investigated the possible correlation between saliva and serum LEV concentrations. Samples of saliva and blood were collected from 30 patients with epilepsy receiving chronic therapy with LEV as monotherapy or add-on therapy, and LEV concentrations were assayed in saliva and serum. Linear regression analyses showed a close correlation between saliva and serum LEV concentrations (r2 = 0.90; P < 0.001). LEV blood and saliva concentrations were linearly related to daily drug doses (r2 = 0.78 and 0.70; P < 0.01). When data were analyzed for subgroups (patients receiving LEV in monotherapy, as add-on therapy with enzyme-inducer AEDs, and as add-on therapy with noninducer or moderate-inducer AEDs), no significant difference was found between saliva and serum LEV concentrations among groups. These preliminary results indicate that LEV, like other AEDs, can be measured in saliva as an alternative to blood-based assays. Saliva LEV collection and assay is a valid noninvasive, more convenient alternative to serum measurement.

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

“…TDM of newer AEDs in saliva has not yet been widely applied [5], but has been studied for six drugs: gabapentin [6], lamotrigine [7], levetiracetam [8], oxcarbazepine (main metabolite 10-hydroxycarbazepine) [9], topiramate [10] and zonisamide [11]. Of these six drugs, gabapentin appears to be clearly unsuited for salivary concentration analysis due to the low concentration in saliva versus plasma (salivary concentrations are ~5–10% that of serum or plasma).…”

Therapeutic Drug Monitoring of Antiepileptic Medications

“…Levetiracetam distribute extensively into saliva, with salivary concentrations usually being slightly higher than serum concentrations in patients receiving chronic therapy (Lins et al, 2007). Salivary and serum levetiracetam concentrations correlate well with one another, making saliva an alternative sample to perform TDM Mecarelli et al, 2007). Levetiracetam shows low binding to serum proteins and has linear pharmacokinetics.…”

“…For drugs with active metabolites (e.g., oxcarbazepine, primidone), TDM can include measurement of the concentrations of both parent drug and its metabolite(s) or just of the metabolite(s). TDM of AEMs in saliva has not yet been widely applied (Liu & Delgado, 1999), but has been studied for ten drugs: carbamazepine (Ruiz et al, 2010;Tennison et al, 2004), gabapentin (Benetello et al, 1997;Berry et al, 2003), lamotrigine (Incecayir et al, 2007;Malone et al, 2006;Ryan et al, 2003), levetiracetam Guo et al, 2007;Mecarelli et al, 2007), oxcarbazepine (Cardot et al, 1995), phenobarbital (Tennison et al, 2004), phenytoin (Tennison et al, 2004), topiramate ), valproic acid (al Za'abi et al, 2003, and zonisamide (Kumagai et al, 1993). Of these ten drugs, gabapentin and valproic acid are clearly unsuited for salivary concentration analysis.…”

Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

“…Several chromatographic methods have been published for quantification of LEV concentrations in biological fluids such as saliva and plasma (or serum) for TDM and in urine for pharmacokinetic aims. They include different subtypes of liquid chromatography with various detection systems (Contin et al, 2008;Grim et al, 2003;Guo et al, 2007;Jain et al, 2006;Juenke et al, 2006;Kuhn, Knabbe, 2013;Lancelin et al, 2007;Martens-Lobenhoffer, BodeBoger, 2005;Matar, 2008;Pucci et al, 2004;Rao et al, 2004;Ratnaraj, Doheny, Patsalos, 1996;Shibata et al, 2012), gas chromatography (Isoherranen et al, 2000;Mecarelli et al, 2007) and microemulsion electrokinetic chromatography (Ivanova et al, 2003). An analytical nonchromatographic method, capillary electrophoresis, is also described (Shihabi, Oles, Hinsdale, 2003).…”

“…Solidphase extractions (SPE) of LEV performed with different polymeric sorbents such as C 18 and hydrophilic-lipophilic balanced copolymer are described in the literature (Isoherranen et al, 2000;Ivanova et al, 2003;Mecarelli et al, 2007;Pucci et al, 2004;Vermeij, Edelbroek, 1994). Protein precipitation is considered a simple, inexpensive and suitable pretreatment procedure especially for drugs minimally bound to plasma proteins.…”