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Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs.
Epilepsia 2010; 51(2):274-9E

Abstract

PURPOSE

Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels.

METHODS

Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control.

RESULTS

Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm].

DISCUSSION

Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.

Authors+Show Affiliations

Neurology Clinic, University of Perugia, Perugia and Fondazione Santa Lucia - IRCCS, Roma, Italy. vincenzobelcastro@libero.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

19780797

Citation

Belcastro, Vincenzo, et al. "Hyperhomocysteinemia in Epileptic Patients On New Antiepileptic Drugs." Epilepsia, vol. 51, no. 2, 2010, pp. 274-9.
Belcastro V, Striano P, Gorgone G, et al. Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs. Epilepsia. 2010;51(2):274-9.
Belcastro, V., Striano, P., Gorgone, G., Costa, C., Ciampa, C., Caccamo, D., ... Pisani, F. (2010). Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs. Epilepsia, 51(2), pp. 274-9. doi:10.1111/j.1528-1167.2009.02303.x.
Belcastro V, et al. Hyperhomocysteinemia in Epileptic Patients On New Antiepileptic Drugs. Epilepsia. 2010;51(2):274-9. PubMed PMID: 19780797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs. AU - Belcastro,Vincenzo, AU - Striano,Pasquale, AU - Gorgone,Gaetano, AU - Costa,Cinzia, AU - Ciampa,Clotilde, AU - Caccamo,Daniela, AU - Pisani,Laura R, AU - Oteri,Giancarla, AU - Marciani,Maria G, AU - Aguglia,Umberto, AU - Striano,Salvatore, AU - Ientile,Riccardo, AU - Calabresi,Paolo, AU - Pisani,Francesco, Y1 - 2009/09/22/ PY - 2009/9/29/entrez PY - 2009/9/29/pubmed PY - 2010/4/16/medline SP - 274 EP - 9 JF - Epilepsia JO - Epilepsia VL - 51 IS - 2 N2 - PURPOSE: Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. METHODS: Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. RESULTS: Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm]. DISCUSSION: Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy. SN - 1528-1167 UR - https://www.unboundmedicine.com/medline/citation/19780797/Hyperhomocysteinemia_in_epileptic_patients_on_new_antiepileptic_drugs_ L2 - https://doi.org/10.1111/j.1528-1167.2009.02303.x DB - PRIME DP - Unbound Medicine ER -