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Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):85-8.

Prolonged use of phenytoin, carbamazepine or valproate monotherapy on plasma levels of folate and B(12): a comparison between epileptic patients with or without cardiovascular disorders.

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Department of Pharmacology and Therapeutics, Arabian Gulf University, Kingdom of Bahrain.



Previous studies showed an association between the blood levels of folate and vitamin B(12) and the risk for cardiovascular disease. The aim of this study is to investigate the effect of chronic use of phenytoin, carbamazepine or valproate monotherapy on the plasma levels of folate and B(12), and to compare folate and B(12) levels in epileptic patients with or without cardiovasular disorders.


The study was conducted in the outpatient neurology clinic at Bahrain Defence Force (BDF) Hospital between January-July, 2005. Medical information was obtained by interviewing the patients and examining their hospital records. Blood folate and vitamin B(12) were measured by Immulite immunoanalysis assay using chemoluminescence.


A total of 26 consecutive outpatients (17 males, 9 females) were recruited in the study. Their mean age +/- SD was 38.2 +/- 20.1 year (range 15-77 year). Five (19.2%) had complex partial epilepsy and the remainder had tonic-clonic seizures. They had epilepsy for 15.7 +/- 8.1 years (range 2-35 years). Thirteen of them used phenytoin, nine carbamazepine and four used valproate. The duration of the treatment (years), dose (mg/day) and serum concentration (micromol/l) were 18.3 +/- 10.6, 376.9 +/- 180.4, 41.6 +/- 25.6, for phenytoin, 14.5 +/- 11.7, 422.2 +/- 175.0, 31.1 +/- 15.9 for carbamazepine and 18.3 +/- 6.3, 400, 567.7 +/- 78.1 for valproate, respectively. Eleven (42.3%) had established cardiovascular disorders such as hypertension, myocardial infarction or stroke. The mean level of plasma folate (12.94 +/- 6.76 ng/ml) and B12 (484.94 +/- 191.25 pg/ml) in epileptic patients with cardiovascular disorders compared to their values (11.27 +/- 5.84), (514.49 +/- 225.31) respectively in epileptics with no cardiovascular disorders were not statistically significant in the two groups.


In epileptic patients on chronic therapy with phenytoin, carbamazepine or valproate folate and B(12) levels were not different in patients with or without cardiovascular disorders.

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