prikaz prve stranice dokumenta Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy
Embargo period 2024-09-01
Scientific paper - Original scientific paper
Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy
European Journal of Clinical Pharmacology, 79 (2023), 8; 1117-1129. https://doi.org/10.1007/s00228-023-03526-z
Božina, Nada; Šušak Sporiš, Ivana; Klarica Domjanović, Iva; Ganoci, Lana; Šimičević, Livija; Lovrić, Mila; Čolak Romić, Zrinka; Petelin Gadže, Željka; Trkulja, Vladimir

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Cite this document

Božina, N., Šušak Sporiš, I., Klarica Domjanović, I., Ganoci, L., Šimičević, L., Lovrić, M. ... Trkulja, V. (2023). Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy. European Journal of Clinical Pharmacology, 79. (8), 1117-1129. doi: 10.1007/s00228-023-03526-z

Božina, Nada, et al. "Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy." European Journal of Clinical Pharmacology, vol. 79, no. 8, 2023, pp. 1117-1129. https://doi.org/10.1007/s00228-023-03526-z

Božina, Nada, Ivana Šušak Sporiš, Iva Klarica Domjanović, Lana Ganoci, Livija Šimičević, Mila Lovrić, Zrinka Čolak Romić, Željka Petelin Gadže and Vladimir Trkulja. "Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy." European Journal of Clinical Pharmacology 79, no. 8 (2023): 1117-1129. https://doi.org/10.1007/s00228-023-03526-z

Božina, N., et al. (2023) 'Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy', European Journal of Clinical Pharmacology, 79(8), pp. 1117-1129. doi: 10.1007/s00228-023-03526-z

Božina N, Šušak Sporiš I, Klarica Domjanović I, Ganoci L, Šimičević L, Lovrić M, and sur.. Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy. European Journal of Clinical Pharmacology [Internet]. 2023 August [cited 2024 April 27];79(8):1117-1129. doi: 10.1007/s00228-023-03526-z

N. Božina, et al., "Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy", European Journal of Clinical Pharmacology, vol. 79, no. 8, pp. 1117-1129, August 2023. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:062920. [Accessed: 27 April 2024]

Metadata
Title (english)Bearing variant alleles at uridine glucuronosyltransferase polymorphisms UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) has no relevant consequences for lamotrigine troughs in adults with epilepsy
AuthorNada Božina
AuthorIvana Šušak Sporiš
AuthorIva Klarica Domjanović
AuthorLana Ganoci
AuthorLivija Šimičević
AuthorMila Lovrić
AuthorZrinka Čolak Romić
AuthorŽeljka Petelin Gadže
AuthorVladimir Trkulja
Author's institutionUniversity of Zagreb
School of Medicine
(Department of Pharmacology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Pharmacology
Abstract (english)
Purpose: To estimate whether epilepsy patients with variant UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) alleles differ from their wild-type (wt) peers in exposure to lamotrigine. Methods: Consecutive adults on lamotrigine monotherapy or lamotrigine + valproate co-treatment undergoing routine therapeutic drug monitoring, otherwise generally healthy and free of interacting drugs, were genotyped for UGT2B7 -161C > T and UGT1A4*3 c.142 T > G. Heterozygous, variant homozygous, or combined heterozygous/variant homozygous subjects were compared to their wt controls for dose-adjusted lamotrigine troughs with adjustment for age, sex, body weight, rs7668258/rs2011425, polymorphisms of efflux transporter proteins ABCG2 c.421C > A (rs2231142) and ABCB1 1236C > T (rs1128503), and level of exposure to valproate using covariate entropy balancing. Results: Of the 471 included patients, 328 (69.6%) were on monotherapy and 143 were co-treated with valproate. Dose-adjusted lamotrigine troughs in UGT2B7 -161C > T heterozygous (CT, n = 237) or variant homozygous (TT, n = 115) subjects were closely similar to those in their wt controls (CC, n = 119): geometric means ratios (GMRs) (frequentist and Bayes) 1.00 (95%CI 0.86-1.16) and 1.00 (95%CrI 0.83-1.22) for CT vs. CC; and 0.97 (0.81-1.17) and 0.97 (0.80-1.20) for TT vs. CC subjects. Lamotrigine troughs were also closely similar in UGT1A4*3 c.142 T > G variant carriers (n = 106: 102 TG + 4 GG subjects) and wt controls (TT, n = 365): GMR = 0.95 (0.81-1.12) frequentist, 0.96 (0.80-1.16) Bayes. GMRs for variant carriers vs. wt controls were around unity also at different levels of exposure to valproate. Conclusion: Dose-adjusted lamotrigine troughs in epilepsy patients with variant UGT2B7 -161C > T or UGT1A4*3 c.142 T > G alleles are equivalent to those in their respective wt peers.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionAccepted version
Journal titleEuropean Journal of Clinical Pharmacology
Numberingvol. 79, no. 8, pp. 1117-1129
p-ISSN0031-6970
e-ISSN1432-1041
DOIhttps://doi.org/10.1007/s00228-023-03526-z
URN:NBNurn:nbn:hr:105:062920
Publication2023-08
Document URLhttps://link.springer.com/10.1007/s00228-023-03526-z
Type of resourceText
Access conditionsEmbargoed access
Embargo expiration date: 2024-09-01
Terms of useLicence In copyright icon
Created on2023-10-02 09:16:15