Antiepileptic Drug Treatment Lowers Coenzyme Q10 Levels in Children.
Abstract number :
3.125
Submission category :
Year :
2001
Submission ID :
623
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
M.V. Miles, PharmD, Child Neurology, Children[ssquote]s Hosp Med Ctr, Cincinnati, OH; P. Tang, PhD, Neurology, Children[ssquote]s Hosp Med Ctr, Cincinnati, OH; P. Steele, MD, Pathology and Laboratory Medicine, Children[ssquote]s Hosp Med Ctr, Cincinnati,
RATIONALE: Increased free radical production is caused by seizure activity, may increase the risk of seizures, and causes some forms of epilepsy. Antiepileptic drugs (AED) may affect the antioxidant system which protects against oxidant stress. Coenzyme Q10 (CoQ), a cofactor in the electron transport chain and an antioxidant, has been suggested to be a useful biomarker of increased oxidative stress. The purpose of this study is to assess the effects of carbamazepine (CBZ), phenytoin (PHT), valproic acid (VPA), phenobarbital (PB), and AED polytherapy on coenzyme Q10 levels in children with epilepsy.
METHODS: After obtaining IRB approval, serum or plasma was obtained from patients who had AED levels ordered for CBZ, PHT, VPA, or PB determination. Blood was also obtained with consent from apparently healthy children having blood collected for routine blood testing. Total CoQ concentrations were measured by HPLC with EC detection (Clin Chem 2001;47:256-265). Total cholesterol, CBZ, PB, PHT, and VPA levels were analyzed by the hospital Clinical Laboratory. ANOVA was used to compare age, total cholesterol, total CoQ, and QCI (CoQ:cholesterol index) differences between groups.
RESULTS: CoQ levels (in 432 children ranging from 1-18 yrs) were measured in 284 patients with epilepsy (99 CBZ, 37 PHT, 5 PB, 100 VPA, and 43 AED polytherapy), in 74 non-epilepsy (psychiatric) patients on VPA, and in 79 healthy controls. Patients receiving PB were excluded because of the small number. Total CoQ levels (mean[plusminus]SD) were lower in the epilepsy patient group (0.63[plusminus]0.22 [mu]g/mL) than in healthy controls (0.80[plusminus]0.27 [mu]g/mL, P[lt].001), and lower than non-epilepsy (VPA) patients (0.73[plusminus]0.24 [mu]g/mL, P[lt].001). CBZ and PHT subgroups also had lower CoQ levels than healthy controls, i.e. 0.64[plusminus]0.21 [mu]g/mL (P[lt].001) for CBZ and 0.51[plusminus]0.24 [mu]g/mL (P[lt].001) for PHT. Cholesterol levels were not significantly different between epilepsy groups, non-epilepsy patients, and healthy controls. QCI results were lower in CBZ patients (0.37[plusminus]0.10), PHT patients (0.33[plusminus]0.09), VPA epilepsy patients (0.44[plusminus]0.14), and AED polytherapy patients (0.38[plusminus]0.10), than in healthy controls (0.53[plusminus]0.17, P[lt].001 for all). Comparison of QCI measurements in (VPA) epilepsy patients with (VPA) non-epilepsy patients (0.45[plusminus]0.13) were not significantly different.
CONCLUSIONS: CoQ levels and QCI were significantly lower in a large cohort of epilepsy patients taking CBZ, PHT, VPA, or AED polytherapy than in healthy controls. QCI were similar in VPA-treated epilepsy and in VPA-treated non-epilepsy patients. Decreased CoQ levels in patients with epilepsy appear to be dependent upon individual AED effect. Further studies are needed to assess the relationship between CoQ and epilepsy-related factors.