ArticleJournal of pain research2022
No Detectable Phenytoin Plasma Levels After Topical Phenytoin Cream Application in Chronic Pain: Inferences for Mechanisms of Action.
Article in Journal of pain research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04647877 (Enrichment Randomized Double-blind, Placebo-controlled Cross-over Trial With PHEnytoin Cream in Patients With Painful Chronic Idiopathic Axonal polyNEuropathy), which is not on this map. Cited by 3 papers.
What it found
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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.
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.
Enrichment Randomized Double-blind, Placebo-controlled Cross-over Trial With PHEnytoin Cream in Patients With Painful Chronic Idiopathic Axonal polyNEuropathy
Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Fast Analgesic Effect in Response Test with Topical Phenytoin Cream Correlates with Prolonged Pain Relief After Extended Use in Painful Diabetic Neuropathy.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Phenotypic Screening of Prospective Analgesics Among FDA-Approved Compounds using an iPSC-Based Model of Acute and Chronic Inflammatory Nociception.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTopical phenytoin can act as an analgesic in chronic pain, but it is unclear if topical phenytoin gives rise to systemic side effects. Therefore, the aim of this study is: 1) to evaluate safety in chronic pain patients who used topical phenytoin up to 30% applied daily on intact skin and mucous membrane, through determining phenytoin plasma levels; and 2) to elaborate on the analgesic mechanism of action. PATIENTS AND
methodsIn this retrospective study, we collected demographic and clinical data from 33 chronic pain patients who used 10% to 30% phenytoin cream, and in whom blood samples were drawn for phenytoin concentration measurement between January 2017 until September 2020. The instruction was to withdraw blood 1 to 4 hours after the last topical phenytoin application. The primary outcome was the detectability of plasma phenytoin after daily use of topical phenytoin.
resultsBlood withdrawal was carried out after on average 14 treatment days with topical phenytoin and on average 2.5 hours after topical phenytoin application. The median daily applied amount of phenytoin cream was 1.2 grams, resulting in a median daily amount of 120 mg phenytoin on the skin. Phenytoin levels were below the limit of detection in all patients and no side effects were reported.
conclusionPlasma phenytoin levels were below the limit of detection after topical use of phenytoin cream formulations up to 30% on intact skin and mucous membrane for the treatment of chronic pain, without side effects emerging. This finding suggests that the mechanism of analgesic action resides in the skin.
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Registered trials
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