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Epilepsy control with carbamazepine monotherapy from a genetic perspective.
BMC Pharmacology & Toxicology 2018 November 16
BACKGROUND: Ethnicity variation is one of the main factors that may affect drug response in clinical practice. As MTHFR gene affects different transcriptome and proteome which affect the clinical response of drugs. Purpose of the current study was to observe possible variations in plasma levels of carbamazepine monotherapy and seizures' control in Pakhtun population of Khyber Pakhtunkhwa (KP) in the context of MTHFR (C677T and A1298C) gene polymorphisms.
METHODS: Blood was collected from the epileptic patients treated with carbamazepine monotherapy for the first time following respective oral doses on its steady state concentration after 3 h of morning dose at 3rd and 6th month of the therapy. Plasma carbamazepine levels were determined using reverse phase high performance liquid chromatography after method validation. MTHFR (C677T, AA298C) gene was genotyped. Patients were followed on 3rd and 6th month of the therapy for monitoring of response to carbamazepine therapy.
RESULTS: Following for 3rd and 6th month of duration of carbamazepine therapy, poor seizure controlled patients were more likely noticed in heterozygous variants (677CT and 1298 AC) of MTHFR gene (P < 0.05). There was no significant (P > 0.05) difference in the dose and plasma level of carbamazepine among different genotypes of MTHFR (C677T and A1298C) gene. Similarly, the difference in dose and plasma level of carbamazepine was not significant (P > 0.05) in the responder and non-responder people with epilepsy.
CONCLUSION: Our study suggests that heterozygous variants of MTHFR (C677T and A1298C) gene are associated with poor seizure control in Pakhtun population of KP despite the fact that plasma level of carbamazepine were found within the therapeutic range.
METHODS: Blood was collected from the epileptic patients treated with carbamazepine monotherapy for the first time following respective oral doses on its steady state concentration after 3 h of morning dose at 3rd and 6th month of the therapy. Plasma carbamazepine levels were determined using reverse phase high performance liquid chromatography after method validation. MTHFR (C677T, AA298C) gene was genotyped. Patients were followed on 3rd and 6th month of the therapy for monitoring of response to carbamazepine therapy.
RESULTS: Following for 3rd and 6th month of duration of carbamazepine therapy, poor seizure controlled patients were more likely noticed in heterozygous variants (677CT and 1298 AC) of MTHFR gene (P < 0.05). There was no significant (P > 0.05) difference in the dose and plasma level of carbamazepine among different genotypes of MTHFR (C677T and A1298C) gene. Similarly, the difference in dose and plasma level of carbamazepine was not significant (P > 0.05) in the responder and non-responder people with epilepsy.
CONCLUSION: Our study suggests that heterozygous variants of MTHFR (C677T and A1298C) gene are associated with poor seizure control in Pakhtun population of KP despite the fact that plasma level of carbamazepine were found within the therapeutic range.
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