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 (2146) nmol/L/mg, and in 14 patients with phenytoin, it was even lower; 17 (13-23) nmol/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.
Böttiger
Y
Y
Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.
Svensson
J O
JO
Ståhle
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology
D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D000077213:Lamotrigine; D010634:Phenobarbital