Lamotrigine in children and adolescents: the impact of age on its serum concentrations and on the extent of drug interactions.
OBJECTIVE
To investigate the impact of age and co-treatment with other drugs on the serum concentrations of lamotrigine in children and adolescents.


METHODS
A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 744 serum samples from 296 subjects (110 males, 186 females, age: 2-19 years) suitable for statistical analysis. The primary outcome variable was the dose-corrected lamotrigine serum concentration, expressed as the lamotrigine concentration/dose (C/D) ratio. A linear mixed model that allowed multiple observations from the same patient was used to identify and quantify the effect of factors influencing the lamotrigine C/D ratio.


RESULTS
According to the model, the lamotrigine C/D ratio decreases by 6% per year of age. Valproate and levetiracetam were found to raise the lamotrigine C/D ratio, whereas the following co-medications reduced it: carbamazepine, clobazam, fluoxetine, clonazepam and ethinyl estradiol. The effect of carbamazepine decreased with increasing age. No gender difference was detected.


CONCLUSIONS
Age is an important factor with respect to the pharmacokinetics and the extent of drug interactions of lamotrigine in children and adolescents. In this population, older individuals will need higher doses than younger ones in order to achieve the same serum concentrations.
Reimers
Arne
A
Department of Clinical Pharmacology, St. Olavs University Hospital, 7006 Trondheim, Norway. arne.reimers@legemidler.no
Skogvoll
Eirik
E
Sund
Janne Kutschera
JK
Spigset
Olav
O
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000928:Antidepressive Agents / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics; D005260:Female; D005473:Fluoxetine / Q000493:pharmacokinetics; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008954:Models, Biological; D014227:Triazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D014635:Valproic Acid / Q000493:pharmacokinetics
D000927:Anticonvulsants; D000928:Antidepressive Agents; D003277:Contraceptives, Oral, Combined; D014227:Triazines; D005473:Fluoxetine; D001569:Benzodiazepines; D004997:Ethinyl Estradiol; D014635:Valproic Acid; D000077213:Lamotrigine