Naslov
Effect of ABC drug transporter genotypes on antiepileptic drug disposition

Autori
Lovrić, Mila ; Božina, Nada ; Hajnšek, Sanja ; Sporiš, Davor ; Lalić, Zdenka ; Granić, Paula

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

Izvornik
Periodicum biologorum. Supplement 1. / Boban, M ; Bradamante, V ; Francetić, I ; Mršić-Pelčić, J ; Muck-Šeler, D ; Pivac, N ; Rošin-Grget, K ; Samaržija, I ; Tvrdeić, A ; Vitezić, D ; Župan, G. - Opatija : Hrvatsko farmaceutsko društvo, 2010, 123-123

Skup
6th Croatian Congress of Pharmacology with International Participation

Mjesto i datum
Opatija, Hrvatska, 15.09.2010. - 18.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
antiepileptics; polymorphisms; ABCB1 genotyping

Sažetak
Introduction: A large number of antiepileptic’s are used to treat epilepsy. Therapeutic monitoring of this disorder is frequent and necessary due to considerable interindividual differences in drug concentrations and efficacy. Along with clinical and exogenous factors, genetic predispositions have been recognized as an important factor in therapy individualization and they take a prominent place in developing algorithms for the selection of the most appropriate drug and dose for each patient. Among pharmacogenetic markers, polymorphic transport proteins, which are responsible for drug transport across various barriers, offered themselves as significant factors of variability and bioavailability of different antiepileptic’s. Transporter proteins that play important role in pharmacokinetics are located in intestinal, renal and hepatic epithelial membranes. ABC transporters such as P-glycoprotein (ABCB1) affect bioavailability of their substrate drugs. The aims of the study were to evaluate the impact of polymorphisms of ABCB1 (C3435T, C1236T, G2677T/A) on antiepileptic drug disposition. We therefore correlated plasma levels of lamotrigine in mono- and polytherapy (carbamazepine, oxcarbazepine, levetiracetame, phenytoin, phenobarbiton, topiramate, valproate) with gene variants. Patients and Methods: A total of 222 epileptic patients, aged 16-76 years, were stratified into lamotrigine monotherapy group (n=58), a group receiving lamotrigine plus inductors (n=98), inhibitors (n=29) or both (n=37). ABCB1 genotyping (C3435T, C1236T, G2677T/A) was performed by Real-time PCR and PCR-RFLP. Therapeutic drug monitoring was performed by HPLC with diode array detector and immunoassay. Results: A statistically significant correlation was confirmed between lamotrigine concentration and additional drugs (p<0.001), type of epilepsy, GGT, ALT, age and weight. Statistical analysis showed correlation between lamotrigine concentration and C1236T and G2677T/A variants of the ABCB1 gene. Lamotrigine concentrations in subjects who were T allele carriers were significantly decreased. Analysis of C3435T variant of the ABCB1 genotype also indicates the tendency of correlation between polymorphism and lamotrigine concentration but this difference was not statistically significant. Conclusion: The obtained results show that ABCB1 polymorphisms exert an influence on antiepileptic drug bioavailability and that they may serve as a pharmacogenetic marker of lamotrigine bioavailability. Due to controversial results reported in literature and a still unclear role of ABC transport proteins in pharmacokinetics of antiepileptic’s, we believe that the obtained results may serve in designing algorithms of antiepileptic drug dosing and as guidelines for further investigations in this field.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija

POVEZANOST RADA