Observational studyBritish journal of clinical pharmacology2018
Interaction between ABCG2 421C>A polymorphism and valproate in their effects on steady-state disposition of lamotrigine in adults with epilepsy.
Observational study in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- ABCG2 Genetic Variability in Drug Exposure and Toxicity: Implications for Clinical Practice.Toxics · 2026Review
- Development of a PBPK Model for Lamotrigine which Incorporates Metabolism by UGT2B10: Impact of UGT2B10 Poor Metabolizer Phenotype and Pregnancy.The AAPS journal · 2025Article
- Challenging pharmacotherapy management of a psychotic disorder due to a delicate pharmacogenetic profile and drug-drug interactions: a case report and literature review.Croatian medical journal · 2024Review
- 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 · 2023Article
- Case report: Interstitial pneumonitis after initiation of lamotrigine.Frontiers in psychiatry · 2023Article
- Pharmacogenetic distinction of the Croatian population from the European average.Croatian medical journal · 2022Article
- Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review.Arhiv za higijenu rada i toksikologiju · 2021Review
- A machine learning approach to personalized dose adjustment of lamotrigine using noninvasive clinical parameters.Scientific reports · 2021Article
- Entry of antiepileptic drugs (valproate and lamotrigine) into the developing rat brain.F1000Research · 2021Article
- Influence of genetic variants and antiepileptic drug co-treatment on lamotrigine plasma concentration in Mexican Mestizo patients with epilepsy.The pharmacogenomics journal · 2020Article
- PharmGKB summary: lamotrigine pathway, pharmacokinetics and pharmacodynamics.Pharmacogenetics and genomics · 2020Review
- Use of pharmacogenomics in elderly patients treated for cardiovascular diseases.Croatian medical journal · 2020Review
- Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy.Frontiers in pharmacology · 2019Article
- Interaction between ABCG2 421C>A polymorphism and valproate in their effects on steady-state disposition of lamotrigine in adults with epilepsy.British journal of clinical pharmacology · 2018Observational
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo investigate the impact of glucuronidation enzyme (UGT1A4*3 142T>G, UGT1A4*2 70C>A, UGT2B7 -161C>T) and transporter (MDR1/ABCB1 1236C>T, ABCG2 421C>A) polymorphisms on steady-state disposition of lamotrigine and on the lamotrigine-valproate interaction.
methodsAdults with epilepsy on lamotrigine monotherapy (n = 131) or lamotrigine + valproate treatment (n = 74) were genotyped and steady-state lamotrigine and valproate morning troughs were determined as a part of routine therapeutic drug monitoring.
resultsNo effect of UGT and MDR1/ABCB1 polymorphisms was observed. In the entire cohort, ABCG2 421A allele had no effect however an interaction between the variant allele and valproate was observed: (i) in lamotrigine-only patients, variant allele (vs. wild type homozygosity) was independently (adjustments: age, sex, body mass index, lamotrigine dose, other polymorphisms) associated with mildly lower lamotrigine troughs [geometric means ratio (GMR) = 0.76, 95% confidence interval (CI) 0.59-0.98], whereas in lamotrigine + valproate patients it was associated with higher troughs (GMR = 1.72, 95%CI 1.14-2.62); (ii) valproate cotreatment was overall associated with markedly higher troughs vs. lamotrigine monotherapy (GMR = 3.49, 95%CI 2.73-4.44), but more so in variant allele carriers (GMR = 5.24, 95%CI 3.38-8.15) than in wild type homozygotes (GMR = 2.32, 95%CI 1.89-2.83); (iii) variant allele effects in two treatment subsets and valproate effects in two genotype subsets differed by 2.36-fold (95%CI 1.39-3.67); (iv) increase in lamotrigine troughs associated with increasing valproate troughs was greater in variant allele carriers than in wild type homozygotes, i.e. variant allele effect increased with increasing valproate troughs.
conclusionThis study is first to indicate a potentially relevant interaction between ABCG2 421C>A polymorphism and valproate in their effects on lamotrigine disposition.
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