Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2018.59.13
Effect of antiepileptic drug comedication on lamotrigine concentrations
Mila Lovrić
; Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia
Ivana Čajić
; Department of Neurology, Referral Centre for Epilepsy, University Hospital Center Zagreb, Zagreb, Croatia
Željka Petelin Gadže
; Department of Neurology, Referral Centre for Epilepsy, University Hospital Center Zagreb, Zagreb, Croatia
Iva Klarica Domjanović
; Agency for Medicinal Products and Medical Devices of Croatia, Zagreb, Croatia
Nada Božina
; Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia
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.
Ključne riječi
Hrčak ID:
200238
URI
Datum izdavanja:
28.2.2018.
Posjeta: 989 *