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Association between lamotrigine concentrations and ABCB1 polymorphisms in patients with epilepsy
Mila Lovrić1, Nada Božina, Sanja Hajnšek
1Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia.
Therapeutic Drug Monitoring
|September 14, 2012
Summary
Genetic variations in the ABCB1 gene influence lamotrigine levels in epilepsy patients. Understanding these ABCB1 polymorphisms aids in personalized anticonvulsant therapy and drug monitoring.
Area of Science:
- Pharmacogenomics
- Clinical Chemistry
- Molecular Biology
Background:
- Epilepsy treatment involves multiple anticonvulsants, necessitating therapeutic drug monitoring.
- Genetic factors, like P-glycoprotein (ABCB1) polymorphisms, affect drug response variability.
- ABCB1 transporter proteins influence the pharmacokinetics of various drugs.
Purpose of the Study:
- To investigate the impact of ABCB1 gene polymorphisms (C1236T, G2677T/A, C3435T) on lamotrigine disposition.
- To correlate ABCB1 variants with lamotrigine plasma concentrations in epilepsy patients.
Main Methods:
- Genotyping of ABCB1 polymorphisms using real-time polymerase chain reaction.
- Quantification of lamotrigine plasma concentrations via high-performance liquid chromatography-diode array detector and immunoassay.
- Recruitment of 222 epilepsy patients on lamotrigine monotherapy or polytherapy.
Main Results:
- Significant correlation between lamotrigine concentration and concomitant medications (P < 0.001).
- ABCB1 C1236T variants showed a correlation with lamotrigine concentrations (P = 0.021) and dose-corrected concentrations (P = 0.017).
- Specific haplotypes (1236C-2677G-3435C) were associated with higher lamotrigine levels compared to other variants (P < 0.001).
Conclusions:
- ABCB1 C1236T, G2677T/A, and C3435T polymorphisms significantly influence lamotrigine serum concentrations.
- These findings highlight the role of pharmacogenetics in optimizing antiepileptic drug therapy.
- ABCB1 genotyping may aid in predicting lamotrigine levels and guiding treatment adjustments.
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