Naslov
Effect of antiepileptic drug comedication on lamotrigine concentrations

Autori
Lovrić, Mila ; Čajić, Ivana ; Petelin Gadže, Željka ; Klarica Domjanović, Iva ; Božina, Nada

Izvornik
Croatian medical journal (0353-9504) 59 (2018), 59; 13-19

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
antiepileptic drug ; comedication ; lamotrigine

Sažetak
Aim: To estimate the effect size of concomitant antiepileptic therapy on the concentrations of lamotrigine, a drug often prescribed in combination with other antiepileptic drugs (AED), which can act as enzyme inducers or inhibitors. Methods: A total of 304 patients with epilepsy, aged 18- 70 years, were divided into a lamotrigine monotherapy group and groups receiving lamotrigine with AEDs that act as enzyme inducers, enzyme inhibitors, or both. We compared lamotrigine monotherapy serum concentrations with those where lamotrigine was administered with a metabolic inhibitor valproate, metabolic inducers carbamazepine, oxcarbazepine, phenobarbital, phenytoin, or topiramate, and both an inducer and an inhibitor. Results: Comparison of trough lamotrigine monotherapy concentrations and lamotrigine polytherapy concentrations showed an almost similar median concentration in case of drug-inducers, and higher lamotrigine concentration in case of comedication with valproate as an inhibitor. A significant difference was confirmed after dose correction (P < 0.001). Significant positive correlations of lamotrigine trough serum concentrations with valproate were observed before and after the dose correction (r = 0.480, P < 0.001 and r = 0.561, P < 0.001, respectively). Positive correlations between the dose-corrected lamotrigine trough concentration and carbamazepine (r = 0.439 ; P < 0.001) or monohydroxy metabolite of oxcarbazepine (MHD) (r = 0.675 ; P < 0.001) were also significant. Conclusion: Higher valproate levels resulted in higher inhibition potency and higher lamotrigine levels. Increased dose-corrected concentrations of inducers carbamazepine and MHD, after the process of induction was finished, did not lower lamotrigine concentrations. These findings can be of clinical significance for optimal AED dosing.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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