Vitamin B&lt;sub&gt;6&lt;/sub&gt; and homocysteine levels in carbamazepine treated epilepsy of Khyber Pakhtunkhwa

Shakir, Shakirullah; Ali, Niaz; Udin, Zia; Nazish, Haleema Rehana; Nabi, Muhammad

doi:10.4314/ahs.v17i2.33

Cited by 3 publications

(6 citation statements)

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“…metabolic effect through deficiency of vitamin B6 that helps in synthesis of inhibitory neurotransmitters. More, in these resistant patients, we found that vitamin B6 level was deficient in heterozygous variants of MTHFR gene [14]. The relation to plasma levels is not so much string as the genotypes are associated with clinical outcomes.…”

Section: Discussionmentioning

confidence: 74%

Epilepsy control with carbamazepine monotherapy from a genetic perspective

Ullah

Ali

2021

Journal of the Neurological Sciences

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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 3 rd and 6 th 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 3 rd and 6 th month of the therapy for monitoring of response to carbamazepine therapy. Results: Following for 3 rd and 6 th 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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Section: Discussionmentioning

confidence: 74%

Epilepsy control with carbamazepine monotherapy from a genetic perspective

Ullah

Ali

2021

Journal of the Neurological Sciences

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“…But we are of opinion that variants (677CT, 677TT and 1298 AC, 1298CC) of MTHFR gene may have association with poor seizure control during carbamazepine therapy in epileptic Pakhtun patients of KP due to indirect metabolic effect through deficiency of vitamin B6 that helps in synthesis of inhibitory neurotransmitters. More, in these resistant patients, we found that vitamin B6 level was deficient in heterozygous variants of MTHFR gene [ 14 ]. The relation to plasma levels is not so much string as the genotypes are associated with clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…[ 13 ]. So far relations have been reported with MTHFR (C677T and A1298C) genotypes polymorphism and elevated levels of homocysteine due to vitamin B6, B12 and folic acid deficiency [ 13 , 14 ]. More, we have recently observed that heterozygous variant (677CT and 1298 AC) of MTHFR gene frequently experienced low level of vitamin B6, which helps in synthesis of GABA, inhibitory neurotransmitters in carbamazepine treated patients.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, we postulated that the said heterozygous variant may be resistant to carbamazepine therapy as a consequence of vitamin B6 deficiency. Thus the current work is carried to correlate the clinical prognosis in heterozygous variant of MTHFR gene and GABRG2 gene, which are deficient in vitamin B6 as per our recently published work [ 14 ]. The pharmacogenomics effect on carbamazepine therapy remains largely unstudied in patients with epilepsies.…”

Section: Introductionmentioning

confidence: 99%

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Epilepsy control with carbamazepine monotherapy from a genetic perspective

Ullah

Ali

Khan

et al. 2018

BMC Pharmacol Toxicol

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BackgroundEthnicity 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.MethodsBlood 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.ResultsFollowing 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.ConclusionOur 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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“…It has been observed prolonged CBZ therapy reduces plasma B6 level significantly. 2,3 Vitamin B 6 plays an important role in treatment of epilepsy. Pyridoxal phosphate, active from of Vitamin B 6 is essential for formation of inhibitory neurotransmitter GABA.…”

Section: Introductionmentioning

confidence: 99%

Microemulsion for Simulataneous Intransal Delivery of Carbamazepine and Vitamin B6 for Treatment of Epilepsy

Acharya¹,

Dave²,

Pundarikakshudu³

et al. 2021

JYP

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Background: Status epilepsy is a neurological emergency characterized by severe bouts of seizure. It has been reported that combination of anti epileptic drug with Vitamin supplements reduce the drug resistance and rapid improvement was also observed in epilepsy patients. In this study, we tried to develop novel intranasal microemulsion for simultaneous delivery of carbamazepine and Vitamin B 6 for treatment of epilepsy. Materials and Methods: For simultaneous estimation of Carbamazepine and Vitamin B 6 , second derivative spectroscopy method was developed and validated. The ME containing CBZ, in lipophilic phase and Vitamin B 6 in aqueous phase was studied for physicochemical characters and ex vivo diffusion through sheep nasal mucosa. The maximal electroshock (MES) induced seizure models was used to establish the pharmacodynamic credentials of the microemulsion. Results: The wavelength selected for Carbamazepine and Vitamin B 6 were 231 nm and 250 nm respectively. It was found that prepared microemulsion is stable with globule size of 395+12 nm. Diffusion across sheep nasal mucosa followed zero order ki netics for carbamazepine and Vitamin B 6 in the prepared microemulsion. It was found that the hind limb extension time and the recovery time were significantly different from control group (p<0.05). The microemulsion remained stable after dilution, centrifugation and freeze thaw cycle as tested for particle size, zeta potential and percentage transmission. Conclusion:The proposed microemulsion should form the basis for treatment of epilepsy which warrants coadministration of micronutrients.

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Vitamin B<sub>6</sub> and homocysteine levels in carbamazepine treated epilepsy of Khyber Pakhtunkhwa

Cited by 3 publications

References 14 publications

Epilepsy control with carbamazepine monotherapy from a genetic perspective

Epilepsy control with carbamazepine monotherapy from a genetic perspective

Epilepsy control with carbamazepine monotherapy from a genetic perspective

Microemulsion for Simulataneous Intransal Delivery of Carbamazepine and Vitamin B6 for Treatment of Epilepsy

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