Evidence map›Paper›PMID 37340142›Full record

ArticleEuropean journal of clinical pharmacology2023

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.

Nada Božina, Ivana Šušak Sporiš, Iva Klarica Domjanović, Lana Ganoci, Livija Šimičević, Mila Lovrić, Zrinka Čolak Romić, Željka Petelin Gadže, Vladimir Trkulja

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In one paragraph

Article in European journal of clinical pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 2 citations in OpenAlex.

  1. Pooled it
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Nada Božina *Department of Pharmacology, Zagreb University School of Medicine, Zagreb, Croatia.ORCID http://orcid.org/0000-0001-6016-1699
Ivana Šušak Sporiš *Department of Neurology, University Hospital Dubrava, Zagreb, Croatia.
Iva Klarica DomjanovićCroatian Agency for Medicinal Products and Medical Devices, Zagreb, Croatia.
Lana GanociDivision of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia.
Livija ŠimičevićDivision of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia.
Mila LovrićAnalytical Toxicology and Pharmacology Division, Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia.
Zrinka Čolak RomićDepartment of Neurology, University Hospital Dubrava, Zagreb, Croatia.
Željka Petelin GadžeDepartment of Neurology, University Hospital Center Zagreb, Zagreb, Croatia.
Vladimir TrkuljaDepartment of Pharmacology, Zagreb University School of Medicine, Zagreb, Croatia. vladimir.trkulja@mef.hr.ORCID http://orcid.org/0000-0002-0968-1194
University Hospital Centre Zagreb · HRUniversity Hospital Dubrava · HRUniversity of Zagreb · HRAgency for Medicinal Products and Medical Devices of Croatia · HR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo 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.

methodsConsecutive 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.

resultsOf 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.

conclusionDose-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.

Indexed as

EpilepsyValproic AcidAdultAllelesAnticonvulsantsBayes TheoremGenotypeGlucuronosyltransferaseHumansLamotriginePolymorphism, Single NucleotideUDP-Glucuronosyltransferase 1A9AnticonvulsantsGlucuronosyltransferaseLamotrigineUDP-Glucuronosyltransferase 1A9UGT2B7 protein, humanValproic AcidBioavailabilityLamotriginePolymorphismUridine glucuronosyltransferases (UGTs)

Identifiers

PMID37340142
OpenAlexW4381333259

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.