PharmGKB summary: lamotrigine pathway, pharmacokinetics and pharmacodynamics

Mitra-Ghosh, Taraswi; Callisto, Samuel P.; Lamba, Jatinder K.; Barbarino, Julia M.; Klein, Teri E.; Altman, Russ B.

doi:10.1097/fpc.0000000000000397

Cited by 24 publications

(44 citation statements)

References 148 publications

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“…37 Gene variants associated with pharmacological responses to drugs are reported in a dedicated database -PharmGKB (https://www.pharmgkb.org) -allowing the identification of relationships between genetic variations (eg, SNPs, indels, repeats, haplotypes) and individual drug responsiveness. 40,41 Herein, in silico pharmacogenetic analysis shows the potential clinical efficacy and/or toxicity of the major drugs selected for Covid-19 treatment. The main drugs proposed for Covid-19 treatments and reference sequence (rs) related to ADRs and efficacy are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…As there is no specific cure for Covid-19, we reviewed all the therapies (drugs) actually in use to counteract SARS-CoV2 effects and the related adverse effects to certain drugs (antiviral, antimalarial, and several biological humanized agents able to reduce the levels of some cytokines belonging to the cytokine storm), as reported by RCTs. [29][30][31][32][33][34][38][39][40][41] Response to these drugs was extremely complex, and numerous cases of toxicities and antiretroviral drug resistance (viral mutations) have been reported. 38 A possible explanation of this variability might be the presence of factors that modify pharmacokinetics/pharmacodynamics and the activity of the virus itself (viral pharmacodynamics).…”

Section: Discussionmentioning

confidence: 99%

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<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

Cafiero¹,

Re²,

Micera³

et al. 2020

PGPM

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The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

Cafiero¹,

Re²,

Micera³

et al. 2020

PGPM

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show abstract

“…We specifically focused on ASMs mainly acting as sodium channel blockers and with a less proven effectiveness in GGE. In this view, lamotrigine (LTG) was excluded from the analysis, given its broader pharmacodynamic spectrum and its more documented efficacy in GGE 24,25 …”

Section: Introductionmentioning

confidence: 99%

Reconsidering the role of selective sodium channel blockers in genetic generalized epilepsy

Irelli

Morano

Fanella

et al. 2021

Acta Neuro Scandinavica

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Objective Selective sodium channel blockers (SSCBs) have a limited use in genetic generalized epilepsy (GGE), due to their well‐known risk of seizure worsening. Although their therapeutic potential in GGE has been suggested by recent evidence, electro‐clinical data supporting their prescription are lacking. We aimed to investigate SSCB safety and effectiveness in a GGE cohort. Methods Subjects who received SSCBs and had ≥5‐year follow‐up were enrolled. Lamotrigine was excluded from analysis due to its broader pharmacodynamic spectrum and its better‐documented efficacy in GGE. Results Fifty‐six patients (median follow‐up 28.5 years) were included. The most used SSCB was carbamazepine in 40 subjects. At the last medical observation, only 9 subjects were still receiving SSCBs. The occurrence of generalized polyspike‐wave discharges (GPSWDs) predicted reduced SSCB retention in Cox multivariate analysis. A seizure reduction ≥50% occurred in 53.5% (30/56) of subjects when considering all seizure types; however, the proportion of responders increased to 67.9% when considering only generalized tonic‐clonic seizures (GTCS). GPSWDs were significantly associated with a reduced response rate, whereas GGE with GTCS only syndrome with a better outcome. The switch from SSCBs to antiseizure medications licensed for GGE improved seizure control in 65% of patients. Seizure worsening was reported in 5/56 patients; juvenile myoclonic epilepsy and a family history of epilepsy were significantly associated with seizure aggravation. Conclusion SSCBs appeared effective on GTCS, but epilepsy aggravation and unsatisfactory control of other seizure types were not uncommon. Our study contributes to identifying new clinical and EEG variables associated with SSCB effectiveness and safety which may help neurologists in patients’ management.

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“…Lamotrigine, originally manufactured as a dihydrofolate reductase inhibitor, is a phenyltriazine‐based antiepileptic drug (AED) which blocks voltage‐gated sodium and calcium channels and is approved by the US Food and Drug Administration (FDA) for focal, generalized tonic‐clonic (GTC), and Lennox‐Gastaut syndrome seizures, as well as type‐1 bipolar disorder 1 2–5 and various extents of neutropenia 3,6–8 …”

Section: Introductionmentioning

confidence: 99%

“…Uridine diphosphate‐glucuronosyltransferase 1A4 (UGT1A4) extensively metabolizes lamotrigine to the inactive 2‐ N ‐glucuronide, predominantly, and 5‐ N ‐glucuronide 1,19 …”

Section: Introductionmentioning

confidence: 99%

Lamotrigine‐induced neutropenia after high‐dose concomitant initiation with phenytoin

Salem

El-Bardissy

2021

Clinical Case Reports

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PharmGKB summary: lamotrigine pathway, pharmacokinetics and pharmacodynamics

Cited by 24 publications

References 148 publications

<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

Reconsidering the role of selective sodium channel blockers in genetic generalized epilepsy

Lamotrigine‐induced neutropenia after high‐dose concomitant initiation with phenytoin

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