Lamotrigine drug interactions in a TDM material

Using therapeutic drug monitoring (TDM) data from our laboratory, we have studied the concentration/dose relationship for lamotrigine and the influence of drug interactions in clinical practice. One hundred forty-nine lamotrigine samples from 104 adult patients were included in the study. The samples were collected as steady state trough values, 9-16 hours after dose intake. Concomitant drug treatment was specified on the analysis request form. Lamotrigine serum concentrations were determined by high-performance liquid chromatography (HPLC). In 20 patients in monotherapy, the concentration/dose (C/D) ratio was 65 (range: 50-84) nmol/L/mg (mean and 95% confidence interval, antilog from lognormal distribution). In 37 patients with concomitant carbamazepine treatment, the C/D ratio was less than half that of the patients in monotherapy; 31 (21-46) nmol/L/mg, and in 14 patients with phenytoin, it was even lower; 17 (13-23) nmoI/L/mg. Valproic acid significantly increased the C/D to 251 (200-320) nmol/L/mg in 13 patients. Triple therapy with Valproic acid and either carbamazepine or phenytoin (23 patients) yielded a C/D slightly above that of monotherapy, whereas a few patients on phenobarbital had a C/D slightly below that of monotherapy. The within-group C/D variation was comparatively small. The C/D ratio in a mixed lamotrigine TDM material shows a widespread intra- and interindividual variation, which can largely be explained by pharmacokinetic interactions with concomitantly used antiepileptic drugs. These results support the use of TDM in lamotrigine therapy.