Multidrug Resistance-1 C3435T Polymorphism and Carbamazepine Plasma Level in Indonesian Temporal Lobe Epilepsy Patients

Abstract

Background: Temporal lobe epilepsy (TLE) has the highest probability of becoming resistant. One of the causes was Polymorphism in multidrug resistant-1 (MDR1) C3435T. In Dr. Cipto Mangunkusumo Hospital, potential drug-resistant epilepsy prevalence was 84.51%; 66.6% of them used carbamazepine (CBZ) as antiseizure medication. This comparative cross-sectional study aimed to investigate MDR1 C3435T polymorphism and CBZ plasma level (plCBZ) in Indonesian TLE patients. Methods: TLE patient was selected consecutively; divided into drug-responsive (DRV) and drugresistant (DRE) groups. Healthy subjects were included as a control for the gene polymorphism comparison. MDR1 was identified using the restriction fragment length polymorphism PCR technique; C allele at 159 and 57bp while T allele at 216bp. High-performance liquid chromatography was used to determine plCBZ. Results: There were 86 subjects; 61 in the study group and 25 controls. The genotype distribution between them was 0.58 vs 0.42, x2=0.54, p=0.000. In the study group, CBZ within therapeutic doses (dCBZ) had outreached the therapeutic plCBZ and found similar in all genotypes. DRE criteria were found in 37 subjects. Distribution of C and T in DRV was 0.63 vs 0.37, x2=10.4; and DRE 0.55 vs 0.45 x2=6.17 (p=0.019). In Tukey’s multiple comparison post hoc test, CT in DRV had significantly lower dCBZ (330,36 ± 174,91 mg) and plCBZ (7.15 ± 2.64 mcg/mL) compared to all genotypes in DRE. Whereas mean dCBZ was around 800mg and plCBZ outreached the toxic level; TT was the highest. Conclusion: The genotype MDR1 distribution was similar in the normal population and DRE. Therapeutic plCBZ was achieved using the low dose. CT genotype responds to lower dCBZ, while TT genotype outreached the highest toxic plCBZ.