Blood Ammonia Level during Valproic Acid Therapy

Background: Valproic acid is an effective drug for controlling seizure in children with epilepsy and it is usually used for treatment as long as two years or more. Blood ammonia level often increased in epileptic children who were treated with long-term valproic acid. The study was conducted to determine the relationship between blood ammonia level with valproic acid therapy in epileptic children.Materials and Methods: This is an observational study with cross-sectional approach. The subjects were 64 children with epilepsy, average age of 6.2 years old. Subjects were 33 boys and 31 girls. Blood ammonia level was examined using enzymatic glutamate dehydrogenase. Subjects were divided into 2 therapeutic groups based on the duration, doses and combination therapy of valproic acid. Subjects were recruited from Pediatric Neurology Clinic, Sanglah General Hospital, Bali, Indonesia, from May to December 2017. Comparison of blood ammonia level between groups were analyzed using an Independent t-test with significances if the p<0.05. Results: A significant difference of blood ammonia level was found between subjects who were treated with valproic acid less than 2 years and more than 2 years (45.7±16.4 mmol/L vs. 70.9±43.6 mmol/L; p=0.032). However, significant difference was not found between the groups according to the doses and combination therapy (p=0.450 and p=0.647, respectively).Conclusion: Blood ammonia level was significantly higher in epileptic children who used long-term valproic acid, hence it was recommended to check the blood ammonia level routinely.Keywords: ammonia, epilepsy, valproic, children

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The Effect of Carnitine Supplementation on Blood Ammonia Level in Epilepsy Children Treated with Valproic Acid: A Randomized Controlled Trial

Molecular and Cellular Biomedical Sciences ◽

10.21705/mcbs.v5i1.177 ◽

2021 ◽

Vol 5 (1) ◽

pp. 18

Author(s):

I Gusti Lanang Sidiartha ◽

I Gusti Ngurah Made Suwarba ◽

Dyah Kanya Wati ◽

Ida Bagus Subanada

Keyword(s):

Valproic Acid ◽

Controlled Trial ◽

Ammonia Level ◽

Control Group ◽

Carnitine Supplementation ◽

Blood Ammonia ◽

Acid Therapy ◽

Blood Ammonia Level ◽

And Control

Background: Long-term use of valproic acid is associated with a high level of blood ammonia related to carnitine deficiency. This study investigates the effect of carnitine supplementation on blood ammonia levels in children with epilepsy who have been treated with valproic acid for more than six months.Materials and Methods: This was a randomized, double-blind, placebo-controlled trial study where children with epilepsy who were treated with valproic acid were randomly allocated to the carnitine supplementation and control group. All children were followed for month, and then measured for blood ammonia level. Blood ammonia levels of both groups were compared using an Independent t-test with a significant of p<0.05.Results: Total of 32 children with epilepsy were enrolled as subjects in this study, with 16 children in carnitine group, and 16 children in control group. Among the subjects, 50% were male and 50% were female, with a mean age of 6.5 years old. The average duration of epilepsy in the carnitine and control group were 41.7 months and 36.9 months, respectively (p=0.419). The duration of valproic acid therapy in the carnitine and control group were 33.1 months and 27.6 months, respectively (p=0.483). The level of blood ammonia in carnitine and control group were 44.6 mg/dL and 81.4 mg/dL, respectively (p=0.007).Conclusion: The level of blood ammonia in a carnitine group was significantly lower than in a control group. It is recommended to give carnitine supplementation in epileptic children treating with long-term valproic acid.Keywords: ammonia, carnitine, epilepsy, seizure, valproic acid

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Association of genetic variants in six candidate genes with valproic acid therapy optimization

Pharmacogenomics ◽

10.2217/pgs.11.64 ◽

2011 ◽

Vol 12 (8) ◽

pp. 1107-1117 ◽

Cited By ~ 36

Author(s):

Chin-Chuan Hung ◽

Jia-Ling Ho ◽

Wei-Lun Chang ◽

John Jen Tai ◽

Tsung-Jen Hsieh ◽

...

Keyword(s):

Valproic Acid ◽

Candidate Genes ◽

Genetic Variants ◽

Acid Therapy ◽

Valproic Acid Therapy

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Thrombocytopenia can occur after several months of valproic acid therapy

Inpharma Weekly ◽

10.2165/00128413-200314100-00042 ◽

2003 ◽

Vol &NA; (1410) ◽

pp. 17

Author(s):

&NA;

Keyword(s):

Valproic Acid ◽

Acid Therapy ◽

Valproic Acid Therapy

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Effect of Valproic Acid Therapy on Zinc Metabolism in Children with Primary Epilepsy

Clinical Neuropharmacology ◽

10.1097/00002826-198702000-00008 ◽

1987 ◽

Vol 10 (1) ◽

pp. 80-86 ◽

Cited By ~ 12

Author(s):

T. Lerman-Sagie ◽

M. Statter ◽

G. Szabo ◽

P. Lerman

Keyword(s):

Valproic Acid ◽

Zinc Metabolism ◽

Acid Therapy ◽

Valproic Acid Therapy

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Blood Ammonia level : Is it a Clue for the Presence of Oesophageal Varices in Cirrhotic Patients ?

Afro-Egyptian Journal of Infectious and Endemic Diseases ◽

10.21608/aeji.2017.16284 ◽

2017 ◽

Vol 7 (4) ◽

pp. 169-176

Author(s):

A.H Lashin ◽

H. M El feky ◽

M.M Elbehisy ◽

M.E Nada

Keyword(s):

Ammonia Level ◽

Oesophageal Varices ◽

Blood Ammonia ◽

Blood Ammonia Level ◽

Cirrhotic Patients

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The Role of Carnitine Supplementation during Valproic Acid Therapy

Annals of Pharmacotherapy ◽

10.1345/aph.19242 ◽

2000 ◽

Vol 34 (5) ◽

pp. 630-638 ◽

Cited By ~ 82

Author(s):

Jackie Y Raskind ◽

Gladys M El-Chaar

Keyword(s):

Valproic Acid ◽

Advisory Committee ◽

Randomized Clinical Trials ◽

Pediatric Population ◽

Carnitine Deficiency ◽

Carnitine Supplementation ◽

Acid Therapy ◽

Pediatric Neurology ◽

Valproic Acid Therapy

OBJECTIVE: To review the pathophysiology and significance of valproic acid–induced carnitine deficiency; to present and evaluate the literature pertaining to carnitine supplementation in pediatric patients receiving valproic acid; and to present the consensus guidelines for carnitine supplementation during valproic acid therapy. DATA SOURCES: A MEDLINE search (1966–December 1998) restricted to English-language literature, using MeSH headings of carnitine and valproic acid, was conducted to identify clinically relevant articles. Selected articles and references focusing on the pediatric population were included for review. DATA EXTRACTION: Study design, patient population, methods, and clinical outcomes were evaluated. DATA SYNTHESIS: Valproic acid, a widely used antiepileptic agent in the pediatric population, is limited by a 1/800 incidence of fatal hepatotoxicity in children under the age of two years. Carnitine is an essential amino acid necessary in β-oxidation of fatty acids and energy production in cellular mitochondria. It has been hypothesized that valproic acid may induce a carnitine deficiency in children and cause nonspecific symptoms of deficiency, hepatotoxicity, and hyperammonemia. Relevant published case reports and trials studying this relationship are evaluated, and a consensus statement by the Pediatric Neurology Advisory Committee is reviewed. CONCLUSIONS: Despite the lack of prospective, randomized clinical trials documenting efficacy of carnitine supplementation in preventing valproic acid–induced hepatotoxicity, the few limited studies available have shown carnitine supplementation to result in subjective and objective improvements along with increases in carnitine serum concentrations in patients receiving valproic acid. The Pediatric Neurology Advisory Committee in 1996 provided more concrete indications on the role of carnitine in valproic acid therapy, such as valproic acid overdose and valproic acid–induced hepatotoxicity. Carnitine was strongly recommended for children at risk of developing a carnitine deficiency. Although carnitine has been well tolerated, future studies are needed to evaluate the efficacy of prophylactic carnitine supplementation for the prevention of hepatotoxicity.

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