Naslov
Influence of UGT2B7 gene polymorphism on lamotrigine and valproate serum concentrations

Autori
Klarica, Iva ; Lovrić, Mila ; Hajnšek, Sanja ; Čajić, Ivana ; Božina, Nada

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract Book of the 14th International Congress of Therapeutic Drug Monitoring & Clinical / - : IATDMCT, 2015

Skup
14th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology

Mjesto i datum
Rotterdam, Nizozemska, 11.10.2015. - 15.10.2015

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
lamotrigine; valproate; UGT2B7; gene polymorphism

Sažetak
Background: Interindividual variability in anti- epileptic drug concentrations remain an important clinical problem. Among pharmacogenetic markers, polymorphic enzymes which are responsible for metabolism could be an important factor for variability in bioavailability of various anticonvulsants. UGT2B7 is involved in valproate and lamotrigine glucuronidation and these drugs are commonly administered in combination. Coadministration of valproic acid is known to increase the area under the plasma concentation time curve (AUC) for lamotrigine. The aim of the proposed research was to investigate the role of UGT 2B7 -161C>T gene polymorphism in interindividual variability of lamotrigine and valproate bioavailability in patients with epilepsy. Patients and methods: A total of 79 epileptic patients, aged 16-76 years, were stratified into a lamotrigine monotherapy group (n=52), and a group receiving lamotrigine plus valproate (n=27). Therapeutic drug monitoring was performed by HPLC with diode array detector for lamotrigine and immunoassay for valproate. Genoytyping of UGT2B7 -161C>T was performed by Taqman real-time PCR method. Results: There was no significant difference in lamotrigine concentrations according to the UGT2B7 -161 C>T genotype, although increased trough concentration values was observed in carriers of the variant allele. The lowest median lamotrigine concentrations were observed in patients with UGT2B7 -161CC genotype (4.6 mmol/L ; 95%CI=1.92- 7.81), while the carriers of one or both varant alleles had higher values (4.9 mmol/L ; 95%CI= 3.4- 11.86 and 7.2 mmol/L, 95%CI=4.56-12.67, respectively). The increasing/upward trend in concentration values remained also after adjusting for dose: 0.0435 (95%CI=0.024-0.103) ; 0.0653 (95%CI=0.051-0.08) and 0.0720 (95%CI=0.044-0.121) mmol/L/mg for -161CC, CT and TT genotype, respectively. There was no evidence of difference between valproate concentrations according to UGT 2B7 -161 C>T genotypes, which could be explained by small sample size and probable influence of CYP2C9 and CYP2C19. Conclusion: The obtained results have shown that UGT2B7 polymorphism may have an influence on lamotrigine plasma concentration and serve as a pharmacogenetic marker of lamotrigine bioavailability.The role of UGT 2B7 for lamotrigine and valproate bioavailability will be confirmed in a larger group of patients, stratified also for CYP2C9 and CYP2C19 genotypes in cases when valproate is also included.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija

POVEZANOST RADA