Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs.
BACKGROUND
Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentrations of LCM in a population of patients with epilepsy.


METHODS
Steady state plasma concentrations of LCM were assessed in a cohort of 75 consecutive patients with epilepsy referred to the Laboratory of Clinical Neuropharmacology for AED therapeutic monitoring over 16 months. Plasma LCM concentrations were measured by high-performance liquid chromatography with spectrophotometric detection.


RESULTS
Median morning trough plasma concentration-to-weight-adjusted dose ratio of LCM [(mg/L)/(mg/kg/d)] was significantly reduced (0.94 versus 1.35, P < 0.001) in patients treated with LCM plus AED strong inducers of cytochrome P450 metabolism, namely, carbamazepine, phenobarbital, and phenytoin (group A, n = 33), compared with a pool of patients not comedicated with AED strong inducers, predominantly including oxcarbazepine, levetiracetam, lamotrigine, and valproic acid (group B, n = 42). The 2 groups were comparable for age, gender, weight, LCM daily dose, and dosing frequency. LCM plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 75 to 600 mg/d, although, at a given drug dose, a large interpatient variability was observed in matched, plasma drug concentration.


CONCLUSIONS
Our findings confirm, in a real-patient clinical setting, preliminary evidence from randomized, clinical trials showing that carbamazepine, phenobarbital, or phenytoin significantly reduces the overall systemic exposure to LCM. From a practical point of view, patients on concomitant AED strong inducers may require a 30% higher dose of LCM compared with patients not receiving strongly inducing AED cotherapy, to achieve the same plasma drug concentration.
Laboratory of Clinical Neuropharmacology, Department of Biomedical and Neuromotor Sciences, University of Bologna and Institute of Research and Treatment (IRCCS), Institute of Neurological Sciences of Bologna, Bologna, Italy.
Manuela
M
Contin
Fiorenzo
F
Albani
Roberto
R
Riva
Carmina
C
Candela
Susan
S
Mohamed
Agostino
A
Baruzzi
D000081:Acetamides / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013053:Spectrophotometry / Q000379:methods; D055815:Young Adult
D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide