1Dept. of Forensic Medicine and Clinical Toxicology, El-Minia University, Egypt.
2Dept. of Pediatric Diseases, El-Minia University, Egypt.
To study the possible antidotal and protective effects of Lcarnitine in acute and chronic valproic acid-induced hepatotoxicity, respectively, in high risk children (age under 24 months)
The current study was divided into 2 parts: Part I (Acute study): 47 children, aging between 9 months to 24 months of both sexes, were divided into 2 groups as follows: Group A: 20 normal healthy children, Group B: 27 children presented with acute VPA intoxication who were received at El-Minia poisoning control centre during the period from the 1st of January 2005 to the 31st of December 2009 and treated with L-carnitine administration at a dose of 600 mg/kg/day L-carnitine intravenously. Part II (Chronic study): 131, children aging between 9 months to 24 months of both sexes, who were received at the outpatient clinic of pediatric diseases in Suzan Mubarak university hospital of Obstetrics, Gynecology and Pediatrics during the period from the 1st of July 2007 to the 30th of June 2009. They were divided into 4 groups as follows: Group I: 20 normal healthy children, Group II: 54 children recently diagnosed as epileptics and were not started any medications yet, Group III: 57 epileptic children treated with VPA for 6 months or more and Group IV: the same 54 children who were diagnosed as epileptics after 6 months of treatment with VPA with L-carnitine supplementation at a dose of 100 mg/kg/day, up to a maximum of 2 g/day. ALT, AST and serum VPA levels were measured in all children underwent the current study.
Results of the acute study revealed that on admission, there was a significant increase of the all measured parameters when compared to the control group and that these parameters were still rising during the 1st 24 hours despite of the starting of L-carnitine administration. Serum transaminases and VPA levels showed a significant decrease after 48h and, more or less, return to the normal ranges after 72h. Results of the chronic study revealed that epilepsy per se has no significant alterative effects on the liver transferases. In the group III, it has been found that the serum VPA level of those patients (87.23 + 7.69 ug/ml) was within the permitted therapeutic serum concentrations range and liver transaminases were significantly increased when compared to those groups I and II. On addition of L-carnitine, a significant decrease of the serum VPA and liver transaminases was reported with no statistically significant difference when compared to those of either the groups I and II.
Our results study suggest that L-carnitine may be a potential antidote for VPA toxicity and a safe prophylactic medical supplementation during VPA therapy in high-risk pediatric patients. It is advised to carry out further controlled, randomized, and multicenter trials to better delineate the therapeutic and prophylactic roles of L-carnitine and the optimal regimen of administration in the management of VPA toxicity either acute or chronic.
L-Carnitine, Valproic Acid, antiepileptic drug, ALT, AST Hepatotoxicity
