Evidence map›Paper›PMID 39658609›Full record

ArticleEuropean journal of pediatrics2024

Effects of CYP2C19 and CYP2C9 polymorphisms on the efficacy and plasma concentration of lacosamide in pediatric patients with epilepsy in China.

Ting Zhao, Hong-Jian Li, Hui-Lan Zhang, Jing Yu, Jie Feng, Long Cui, Ke-Fang Sun, Yan Sun, Lu-Hai Yu

Abstract readMulticenter Study
PubMed Publisher
In one paragraph

Article in European journal of pediatrics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
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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.

Ting Zhao *Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China.
Hong-Jian Li *Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China.
Hui-Lan ZhangDepartment of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China.
Jing YuDepartment of Pediatrics, Children's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hospital of Beijing Children's Hospital, Urumqi, 830001, Xinjiang, China.
Jie FengDepartment of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China.
Long CuiDepartment of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China.
Ke-Fang SunMedicine, Zhejiang University School, Hangzhou, Zhejiang, China.
Yan SunDepartment of Pediatrics, Children's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hospital of Beijing Children's Hospital, Urumqi, 830001, Xinjiang, China. sunkefang@163.com.
Lu-Hai YuDepartment of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China. 1523264450@qq.com.

Funding

Natural Science Foundation of Xinjiang Uygur Autonomous Region 2022D01C154
6 · The paper itself

Abstract

To evaluate the effects of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19) polymorphisms on the plasma concentrations, efficacy, and safety of lacosamide (LCM) among pediatric patients with epilepsy. This prospective study was conducted at two institutions. It included 215 pediatric patients with epilepsy who were under LCM. LCM plasma concentrations were quantified using validated ultra-performance liquid chromatography. CYP2C9 and CYP2C19 polymorphisms were analyzed in all pediatric patients in our hospital's Institute of Clinical Pharmacy research laboratory through polymerase chain reaction, agarose gel electrophoresis detection, gel recovery, and other steps. Seizure frequencies were recorded 3, 6, and 12 months after initiating LCM therapy and compared with the baseline monthly frequency. Clinical information, including efficacy, toxicity, and concomitant drugs, was collected. A total of 158 pediatric patients (73.5%) responded to LCM therapy. Of them, 77 patients reported adverse events while under LCM. The LCM plasma concentration was linearly correlated with its daily dose (r = 0.26, p < 0.001). Patients with adverse events reported higher LCM plasma concentrations (7.9 ± 4.0 µg/mL) than patients without adverse events (6.8 ± 3.0 µg/mL; p < 0.05). The poor metabolizer (PM) group demonstrated the highest concentration-to-dose ratio (1.7 ± 0.7 μg·mL

conclusionLCM plasma concentrations were strongly associated with its clinical efficacy and toxicity. CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in pediatric patients with epilepsy. CYP2C19 PMs with two no-function alleles are likely to have higher LCM plasma concentrations. WHAT IS KNOWN: • LCM is metabolized by CYP2C19, CYP2C9, and CYP3A4 into pharmacologically inactive O-desmethyl-lacosamide; it primarily undergoes renal elimination. • Plasma LCM concentrations in patients treated with the recommended dose vary widely between and within individuals variability. WHAT IS NEW: • CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in Chinese pediatric patients with epilepsy. • CYP2C19 PMs with two no-function alleles are likely to have higher plasma LCM concentrations.

Indexed as

AnticonvulsantsCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9EpilepsyLacosamidePolymorphism, GeneticAdolescentChildChild, PreschoolChinaFemaleGenotypeHumansInfantMaleProspective StudiesAnticonvulsantsCYP2C19 protein, humanCYP2C9 protein, humanCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9LacosamideCYP2C19CYP2C9EfficacyLacosamidePlasma concentrationSafety

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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.