Bioactivation of a Toxic Metabolite of Valproic Acid, (E)-2-Propyl-2,4-pentadienoic Acid, via Glucuronidation. LC/MS/MS Characterization of the GSH−Glucuronide Diconjugates†

1996 ◽  
Vol 9 (2) ◽  
pp. 517-526 ◽  
Author(s):  
Wei Tang ◽  
Frank S. Abbott
Keyword(s):  
Valproic Acid ◽  
Toxic Metabolite ◽  
Pentadienoic Acid

Synthesis and characterization of valproic acid ester pro-drug micelles via an amphiphilic polycaprolactone block copolymer design

2015 ◽  
Vol 6 (13) ◽  
pp. 2386-2389 ◽  
Author(s):  
Suchithra A. Senevirathne ◽  
Suthida Boonsith ◽  
David Oupicky ◽  
Michael C. Biewer ◽  
Mihaela C. Stefan
Keyword(s):  
Valproic Acid ◽  
Block Copolymer ◽  
Block Copolymers ◽  
Histone Deacetylase ◽  
Hdac Inhibitors ◽  
Research Direction ◽  
Synthesis And Characterization ◽  
Covalent Bonds ◽  
New Research

The attachment of Histone deacetylase (HDAC) inhibitors via covalent bonds to biocompatible and biodegradable block copolymers provides a new research direction for cancer treatment.

scholarly journals The High Incidence of Valproate Hepatotoxicity in Infants May Relate to Familial Metabolic Defects

1990 ◽  
Vol 17 (2) ◽  
pp. 145-148 ◽  
Author(s):  
R.E. Appleton ◽  
K. Farrell ◽  
D.A. Applegarth ◽  
J.E. Dimmick ◽  
L.T.K. Wong ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Fatty Acid ◽  
Developmental Delay ◽  
Hepatic Failure ◽  
Metabolic Disorders ◽  
Acid Oxidation ◽  
Toxic Metabolite ◽  
Metabolic Defects ◽  
Intractable Seizures ◽  
High Incidence

ABSTRACT:The incidence of fatal hepatic failure associated with valproic acid (VPA) therapy is highest in children under the age of three years, particularly in those with developmental delay. The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation. We describe two unrelated infants with developmental delay who developed hepatic failure while receiving VPA. Siblings of both children subsequently developed hepatic steatosis and intractable seizures without being exposed to VPA. This suggests that that the two children who developed liver failure when receiving VPA may have had a familial metabolic disorder. Familial metabolic disorders may account partly for the higher incidence of fatal hepatotoxicity described in infants receiving VPA.

Cytochrome P-450--catalyzed formation of delta 4-VPA, a toxic metabolite of valproic acid

Science ◽  
1987 ◽  
Vol 235 (4791) ◽  
pp. 890-893 ◽  
Author(s):  
A. Rettie ◽  
A. Rettenmeier ◽  
W. Howald ◽  
T. Baillie
Keyword(s):  
Valproic Acid ◽  
Toxic Metabolite ◽  
Cytochrome P 450

Characterization of Inhibitory Effect of Carbapenem Antibiotics on the Deconjugation of Valproic Acid Glucuronide

2010 ◽  
Vol 38 (10) ◽  
pp. 1828-1835 ◽  
Author(s):  
Yusuke Masuo ◽  
Kousei Ito ◽  
Takehito Yamamoto ◽  
Akihiro Hisaka ◽  
Masashi Honma ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Inhibitory Effect

scholarly journals L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report

2017 ◽  
Vol 45 (3) ◽  
pp. 1268-1272 ◽  
Author(s):  
Cecilia Maldonado ◽  
Natalia Guevara ◽  
Alicia Silveira ◽  
Pietro Fagiolino ◽  
Marta Vázquez
Keyword(s):  
Valproic Acid ◽  
Seizure Control ◽  
Urea Cycle ◽  
Therapeutic Option ◽  
Rare Condition ◽  
Ammonia Level ◽  
Toxic Metabolite ◽  
Carnitine Supplementation ◽  
Carnitine Level ◽  
Psychiatric Setting

Valproic acid is a broad-spectrum anticonvulsant that has also gained attention in the psychiatric setting. With respect to safety, valproic acid may induce a seemingly rare condition, hyperammonemia, which can induce a wide variety of symptoms ranging from irritability to coma. The proposed mechanism of hyperammonemia involves depletion of carnitine and overproduction of a toxic metabolite, 4-en-valproic acid, both of which impair the urea cycle and thus ammonia elimination. Carnitine is a commonly used antidote for acute intoxication of valproic acid, but is not a therapeutic option for management of chronic adults with adverse effects related to valproic acid. We herein report a case involving a woman with epilepsy who developed hyperammonemia after a change in her anticonvulsant therapy. She reported increased seizures and gastrointestinal disturbances. Her ammonia, valproic acid, 4-en-valproic acid, and carnitine levels were monitored. Her ammonia level was elevated and her carnitine level was at the inferior limit of the population range. She was supplemented with carnitine at 1 g/day. After 1 month, her ammonia level decreased, her carnitine level increased, and her seizures were better controlled. Carnitine supplementation was useful for reversal of her hyperammonemia, allowing her to continue valproic acid for seizure control.

Theoretical characterization of SOME amides and esters DERIVATIVES of valproic acid

2009 ◽  
Vol 16 (2) ◽  
pp. 343-359 ◽  
Author(s):  
Nieves C. Comelli ◽  
Patricio Fuentealba ◽  
Eduardo A. Castro ◽  
Alicia H. Jubert
Keyword(s):  
Valproic Acid ◽  
Theoretical Characterization ◽  
Derivatives Of

Toxigenicity of Trichothecium roseum link: Isolation and partial characterization of a toxic metabolite

1969 ◽  
Vol 39 (3-4) ◽  
pp. 231-240 ◽  
Author(s):  
J. L. Richard ◽  
G. W. Engstrom ◽  
A. C. Pier ◽  
L. H. Tiffany
Keyword(s):  
Partial Characterization ◽  
Toxic Metabolite ◽  
Trichothecium Roseum
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