Effects of l-carnitine supplementation in patients with childhood-onset epilepsy prescribed valproate

Okumura, Akihisa; Takagi, Mizuki; Numoto, Shingo; Iwayama, Hideyuki; Azuma, Yoshiteru; Kurahashi, Hirokazu

doi:10.1016/j.yebeh.2021.108220

Cited by 5 publications

(2 citation statements)

References 36 publications

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“…The formation of acetyl-CoA allows the formation of NAGA and the subsequent detoxification of ammonia to urea, thereby correcting hyperammonemia. L-carnitine supplementation is well tolerated, and reports of possible ADRs are rare [ 38 , 133 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic and Toxic Effects of Valproic Acid Metabolites

et al. 2023

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Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: β-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient’s pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine).

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Section: Discussionmentioning

confidence: 99%

Therapeutic and Toxic Effects of Valproic Acid Metabolites

et al. 2023

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“…This mechanism is theorized to reduce brain edema and treat valproate-induced encephalopathy [7,9]. There is data supporting using L-carnitine as chronic supplementation in patients prescribed valproate [10,11]. However, the literature is mixed on the efficacy of using L-carnitine for acute toxicity.…”

Section: Current Literature On Treating Valproate Toxicitymentioning

confidence: 99%

Valproate-Induced Encephalopathy Presenting at Therapeutic Blood Concentrations: A Case Report and Literature Review

Pavar¹,

Xu²,

Sawar³

et al. 2023

Cureus

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Patients presenting with hyperammonemic encephalopathy are likely to have hepatic encephalopathy. However, valproate (an anticonvulsant and mood stabilizer) can also cause hyperammonemic encephalopathy and belongs on the differential for patients taking it, especially if there are recent contributory medication changes. We present a case report of a 61-year-old woman with valproate-induced hyperammonemic encephalopathy but with an initial valproate level within the therapeutic range (50-100 mcg/dL). After withholding valproate and before additional treatment could be initiated, she became fully alert and oriented. We present a literature review exploring valproate toxicity and treatment. Our case shows that clinical suspicion for valproate-induced hyperammonemic encephalopathy is warranted even if the valproate level is within the therapeutic range.

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