| PART 1:Development and Validation of Novel Methods for Antiepileptic Drugs CarbamazepineBackground:Carbamazepine has complicated pharmacokinetic characteristics leading to variation in plasma concentration level,which requires monitoring of drug concentration routinely to ensure its maximum efficacy,safety and to prevent adverse effects.Objective:This research study is aimed to establish and validate a quick,precise,more efficient,easily accessible,novel,highly sensitive and cost-effective assay liquid chromatography/mass spectrometry technique for providing a fast,accurate and reliable carbamazepine plasma drug concentration results.Methods:The mobile phase selected for this assay method was ammonium acetate(5mM),methanol(40:60 v/v).Agilent LC/MS system was used.For separation of analytes,diamonsil C18 column(150mm×4.6mm,5μm)was selected.The blood of each patient was drawn at trough level in Qilu Hospital of Shandong University.A total of 103 blood samples from epileptic patients were collected for the measurement of carbamazepine plasma concentration with validated LC/MS assay method.Simple protein precipitation method was selected for extraction of analytes.Results:The decent linear curve in the range of 5-1000ng/ml with linearity equation of y=2.445 16x +0.00348175 and correlation coefficient(R2)of 0.99881 was obtained.The results revealed that all analytical validation parameters which were performed were within the accepted range of International Conference on Harmonisation guidelines.Conclusion:This is a simple,quick,accurate,sensitive,cost-effective,novel and precise LC/MS method with a simple extraction procedure,less plasma volume and low limit of quantitation was developed,validated and productively utilized in the 103 epilepsy patients in drug monitoring of carbamazepine.This assay technique can also be applied in other clinical applications such as pharmacokinetics,toxicokinetics and bioequivalence studies.PhenytoinBackground:The narrow therapeutic range of phenytoin,non-linear pharmacokinetics,inconsistent absorption,the unpredictable association between dose and concentration of phenytoin and noteworthy clinical drug interactions,support the necessity of drug monitoring in epilepsy sufferers to individualize and sustain therapy.It is very difficult to use one assay method which is simple,quick,precise,easily accessible,cost-effective and highly sensitive for therapeutic drug monitoring of phenytoin because some of the available methods are complex,expensive and not easily available in small laboratories.On the other hand,available simple,inexpensive and rapid assays are inaccurate,unreliable and not sensitive enough.Physicians and clinicians have to wait long for getting reliable therapeutic drug monitoring results of phenytoin for making rational and immediate clinical decision.The rational and immediate decision is key and essential in epileptic patients.Objective:This research work is planned to establish and validate a quick,precise,more efficient,easily accessible,novel,highly sensitive and cost-effective assay liquid chromatography-mass spectrometry technique for providing quick,accurate and reliable phenytoin drug concentration results.Methods:The mixture of mobile phase was Ammonium acetate(5Mm):Methanol in the ratio(35:65 v/v).Agilent LC/MS system was used.Analytes in plasma were extracted on Diamonsil C18(150mm×4.6mm,5μm)column by the simple protein precipitation method.A total of 27 blood samples were received for drug monitoring of phenytoin.The blood sampling of 27 patients with epilepsy was drawn out in Qilu Hospital Jinan,China.Results:An excellent and linear curve was obtained with(R2)>0.999 over the concentration range of 0.2-20 μg/mL.The outcomes revealed that all analytical validation parameters which were performed were within the accepted range of International Conference on Harmonisation guidelines.Conclusion:A simple,quick,cost-effective,precise,novel,extremely sensitive,easily usable LC/MS technique was established,validated and productively employed in phenytoin TDM.Surprisingly it was observed that almost all the patients’ phenytoin plasma results were out of reference range with the exception of two patients whose phenytoin plasma concentrations were in the reference range.However,further investigations are required.The proposed method is rapid and reliable.Therapeutic drug monitoring results were readily available to physicians and clinicians for making the rational and immediate decision and more importantly due to the rational decision of neurologists;epileptic patients can control the symptoms of disease successfully with minimal cost of phenytoin monitoring by avoiding unnecessary visits to hospitals for unreliable and needless repeated processes of drug monitoring.This assay method can also be applied in other clinical applications such as pharmacokinetics,toxicokinetics and bioequivalence studies.LamotrigineBackground:Spikes in Lamotrigine concentrations levels and associated clinical toxicity may occur unpredictably.Objective:This study indicates the establishment and authentication of a simple,sensitive,rapid,an accurate,novel and economical assay for measuring lamotrigine plasma concentration levels in epileptic patients with high pressure liquid chromatography-ultraviolet detection.Methods:The analytes from plasma were extracted with methanol by the protein precipitation method and separated on the analytical column Diamonsil C18(150mm×4.6mm,5μm)Waters-Milford,MA,United States.The mobile phase selected for this assay method was Trifluoroacetate(0.1%),Methanol(59:41 v/v).The 1.5 ml/min as an isocratic flow rate was applied and 260nm of a wavelength selected.Results:The standard curve of lamotrigine presented excellent linearity in the 1.0-50μg/mL concentration range with(r2=0.9961),and concentration of L0μg/ml was found as the lower limit of quantification.The results revealed that all analytical validation parameters which were performed were within the accepted range of International Conference on Harmonisation guidelines.Conclusion:The simple,sensitive,quick,rapid and environment-friendly high pressure liquid chromatography technique for the quantification of Lamotrigine in epileptic patients was demonstrated,validated and successfully utilized in monitoring drug concentration of lamotrigine in the plasma of sixty-seven epilepsy patients who were using Lamotrigine.The stated technique can be easily applied to the routine therapeutic monitoring of lamotrigine.In addition to the therapeutic drug monitoring,the indicated method can be also very useful for bioequivalence studies,pharmacokinetics studies,toxicokinetics studies and pharmacovigilance studies.LevetiracetamBackground:Levetiracetam is an antiepileptic drug with serious and life-threatening toxic effects.These effects could result in a decrease in the count of red blood cells,neutrophils and hematocrit.Asthenia,somnolence,and dizziness are also some of the toxicities connected to levetiracetam usage.These adverse effects may be associated with the levetiracetam plasma concentration.Objective:This study indicates the establishment and authentication of a fast,simple,sensitive,reliable,economical,novel and accurate technique for quantifying levetiracetam concentration by employing high pressure liquid chromatography-ultraviolet detection.Methods:The combination of the mobile phase was sodium dihydrogen phosphate(0.2 mol/L and pH of 4.5)and acetonitrile(90:10,volume/volume mixture).The 1.2ml/min as an isocratic flow rate and wavelength was adjusted to 210nm.The analytical column used for separation was diamonsil C18(5μm,200mm×4.6mm),Waters-Milford,MA,US.The analyte from plasma was extracted with the simple liquid-liquid extraction method.A 500 uL sample of pre-treatment plasma was doped with internal-standard caffeine.Results:The calibration curve of levetiracetam displayed outstanding linearity within(1-160μg/mL)concentration range,and a correlation of coefficient was 0.999.The lowermost concentration of quantitation was 1μg/mL.The assay method displays a decent intra-assay and interassay precision(less than 7%)and having ideal extraction efficiency/recovery,80%for levetiracetam and 101%for Internal Standard.The stability results were also within acceptable limits.The results revealed that all analytical validation parameters which were performed were within the accepted range of International Conference on Harmonisation guidelines.Conclusion:A more simple,reliable,highly sensitive,cost-effective and quick assay technique to quantify levetiracetam was established and corroborated in human plasma with the stated procedures.The stated assay is useful in the routine determination of levetiracetam in epileptic patients.Besides therapeutic drug monitoring;this assay method can also be applied in other clinical applications such as pharmacokinetics,toxicokinetics and bioequivalence studies.PART 2:Therapeutic Drug Monitoring(TDM)of Carbamazepine and Phenytoin with Modern Techniques(Enzyme-multiplied Immunoassay Techniques)and Evaluation of Correlation of Developed and Validated Novel(LC/MS)Methods to quantify Carbamazepine and Phenytoin with Enzvme-multiplied Immunoassay Techniques(EMIT)for TDMCarbamazepineBackground:Carbamazepine has variable pharmacokinetic characteristics which may easily cause variation in plasma levels of carbamazepine.Therefore,routine determination of drug concentration is needed in order to get maximum efficacy,safety and avoid toxicity.Numerous precise and highly sensitive chromatographic techniques have been reported for therapeutic monitoring of carbamazepine but these assay methods are complicated and costly.Immunoassay techniques such as enzyme-multiplied immunoassay techniques are simple,rapid and easy to operate.They are used very often in the routine therapeutic monitoring of carbamazepine.Objective:The present work is aimed at assessing the correlation of LC/MS technique with EMIT for measuring routine drug monitoring of carbamazepine in the blood of patients with epilepsy.Methods:The correlation of two stated methods for routine drug measurement of carbamazepine was studied and compared.Overall 103 samples of blood were received from epilepsy patients for determination of the carbamazepine.The regression equation and Bland-Altman plot with the software of MedCalc and SPSS were used respectively for evaluating the correlation in 93 epilepsy patients.Results:The correlation of LC/MS technique with EMIT was very good(R2= 0.971)but enzyme-multiplied immunoassay technique determination concentration results of carbamazepine in plasma were a little higher than the concentration results of carbamazepine obtained with LC/MS.Conclusion:The relationship between the LC/MS technique and EMIT was studied and compared.There were no significant differences in the two methods.The liquid chromatography-mass spectrometry method is more accurate and highly reliable.Nevertheless,a good correlation was found between the LC/MS technique with EMIT.Enzyme-multiplied immunoassay technique is much simpler,quicker and less expensive.The results can be accessed on the same day and can also be suitably utilized in carbamazepine monitoring.PhenytoinBackground:Phenytoin is the drug of narrow therapeutic range.There is a strong evidence of phenytoin being life-threatening and causing dangerous cutaneous adverse reactions which are often reported in the Chinese population suggesting that the Chinese people are at higher risk of developing more serious adverse effects when they use phenytoin.Objective:The current work is intended to study the correlation of chromatographic(LC/MS)with immunoassay(EMIT)methods in the quantification of phenytoin plasma concentration in epileptic victims and to provide a guideline for clinical and pathological laboratories which are engaged in routine therapeutic drug monitoring of phenytoin.Methods:Total 27 epilepsy patients were received for determination of plasma phenytoin concentration and determination of phenytoin plasma concentration was performed with two methods.i.e.LC/MS and EMIT.All samples were collected in Qilu Hospital of Shandong University and research work was performed with Declaration of Helsinki.Results:A good and decent linear curve in 0.2-20 p.g/mL for liquid chromatography/mass spectrometry and 2.5-40 μg/mL concentration ranges for enzyme-multiplied immunoassay technique respectively was obtained.The correlation of chromatographic;LC/MS with immunoassay;EMIT method in determination of phenytoin was good(R2= 0.921).Phenytoin plasma concentration determined by enzyme-multiplied immunoassay technique was slightly lower than liquid chromatography/mass spectrometry.There was a 95%confidence interval which was-21.4～4.3 μg/mL.Both of the methods were suitable for determining phenytoin concentrations in epileptic patients.Conclusion:The correlation between the two methods was very good but phenytoin concentration determined by liquid chromatography/mass spectrometry was a little higher than enzyme-multiplied immunoassay technique.However,its clinical significance needs further evaluation.PART 3:Assessment of the Relationship between Plasma Concentrations of Carbamazepine,Phenytoin and Valproic Acid with Clinical Response,Safety and Toxicity in Different Age and Gender Groups of Chinese Epileptic Patients with the Applications of TDMCarbamazepineBackground:Carbamazepine is a regularly prescribed and recommended antiepileptic drug for epileptic patients.The influence of genetic differences,sex,age and race on the carbamazepine plasma levels and its metabolites is well recognized.Objective:The intention of this work is to quantify the carbamazepine plasma concentration and to evaluate and compare the clinical response,compliance,safety,and toxicity in different age and gender groups of Chinese epileptic patients on the basis of therapeutic drug monitoring results of carbamazepine,since Han-Chinese people are at greater danger of developing serious and fatal adverse effects when exposed to carbamazepine.Methods:The plasma concentration results of carbamazepine in epileptic patients,obtained with validated methods were compiled,evaluated and compared for compliance,safety and toxicity in different age and gender groups of Chinese epileptic patients.The therapeutic drug monitoring results of males and females were separately compiled and thereafter each gender group was further divided into children,adults and elderly as different age group.All age groups in both gender groups were evaluated for therapeutic,sub-therapeutic and toxic ranges.Results:In this study,45%of total samples had sub-therapeutic levels and 55%of all samples had carbamazepine levels in therapeutic range.None of the gender and age groups was found in toxic-range.Compared to males,female samples were.more in a number of sub-therapeutic levels.Populations of male children and female children had more samples in sub-therapeutic levels as compared to adult and elderly males,and adult and elderly females,respectively.However,this requires further evaluation.Conclusion:The outcomes of this study revealed that majority of patient samples of carbamazepine plasma concentration results were in sub-therapeutic levels and an inappropriate clinical response was noticed in these patients.It is suggested that regular drug monitoring of carbamazepine must be performed to get a maximum clinical response and to evaluate the compliance,optimize the efficacy and safety and to minimize the toxicity.The dose of carbamazepine in epileptic patients should be adjusted only after therapeutic drug monitoring results.PhenytoinBackground:The narrow therapeutic index,non-linear pharmacokinetics,and unpredictable absorption require regular therapeutic monitoring of phenytoin.The influence of genetic differences,sex,age and race on the phenytoin plasma levels and its metabolites is well recognized.Objective:This study is at aimed at evaluating phenytoin plasma drug concentration and its relationship with clinical response,persistent seizures,and toxicity in different gender and various age groups of Chinese epileptic patients.Methods:Forty-Eight epileptic patients displaying persistent seizures or suspected of adverse effects were requested for phenytoin drug monitoring by the Neurology Department of Qilu Hospital.All these samples were analyzed for therapeutic drug monitoring with Enzyme-multiplied immunoassay technique.Results:Surprisingly it was found that majority of 85.5%samples were out of the reference range,of which 69%of samples were in sub-therapeutic levels and 16.5%of samples had toxic levels and an unfavorable clinical response was noticed in these patients.Only 14.5%of all testing samples had plasma concentration levels of phenytoin in the therapeutic levels.The difference in plasma concentration of phenytoin is notably altered in different gender and various age groups.Compared to males and compared to adult patients,females and children patient samples had an increased number of out of reference range.Conclusion:The outcomes of this study stated that majority of patients therapeutic results were out of the reference range and an unfavorable clinical response was noticed in these patients.We speculate that persistent seizures or toxicity and unfavorable clinical response in most of these patients may be most probably because of out of therapeutic range of phenytoin.The main reasons for the out of therapeutic range and unfavorable clinical response in these patients may be due to poor compliance,underdose,overdose or improper self-dosage taken by patients themselves.Other factors such as genetic factors,variations in genetic polymorphism,intra and inter-individual variations in pharmacokinetics parameters,pathological conditions,pharmacokinetics interactions and special conditions such as pregnancy and age-related body response to the drugs may also cause the variations in plasma concentration and therapeutic response.Children and infants are unique groups because of the rapid metabolic rate and rapid elimination time and larger volume of distribution values and females also have rapid metabolic rate and rapid elimination during pregnancy.These factors in children,infants and females may also be responsible for sub-therapeutic levels.However,all these factors require further vigilant evaluation.Careful attention must be applied to specific gender and particular age group on the individual basis in the interpretation of plasma concentration results,in order to facilitate the modification of doses and develop the best approach in treatment and to obtain the desired clinical response because multiple factors can affect the phenytoin plasma concentration.Through these results,it can be concluded that a good correlation exists between phenytoin plasma concentration and clinical response.Therefore regular therapeutic monitoring of phenytoin and screening of HLA-A,B,C and DRB1 genotypes before prescribing phenytoin in epileptic patients is essentially required to achieve maximum clinical response and prevent the serious toxicity.Valproic AcidBackground:The unpredictable and unfavorable connection of dose and plasma concentration of Valproic acid supports the necessity to regularly measure its plasma concentration.Objective:The present study is drug monitoring of valproic acid and comparative evaluation of therapeutic monitoring results of valproic acid for assessment of clinical response,compliance,safety and toxicity in different age and gender groups of Chinese epileptic patients.Methods:A total of 206 plasma samples(126 males and 80 females)of epileptic patients receiving valproic acid with persistent seizures and suspected of adverse effects or non-compliance were advised to do therapeutic drug monitoring of valproic acid by neurology department of Qilu Hospital,Jinan,China.The drug monitoring results of valproic acid were analyzed with Enzyme-multiplied immunoassay technique.All drug monitoring results were compiled,evaluated,and also compared for compliance,safety,and toxicity in different age and gender groups of epileptic patients.The males and females were separated and thereafter each gender group was further divided by age groups into infants,children,adults and elderly.All age groups in both gender groups were evaluated for therapeutic,sub-therapeutic and toxic ranges.Results:It was found that 29%of the total samples were found in sub-therapeutic levels,13%of the samples had toxic levels and 58%of all the samples had valproic acid levels in therapeutic range.The unfavorable clinical response was the main reason for monitoring of valproic acid plasma concentrations in these all patients.Female samples were more in a number of sub-therapeutic levels compared to male samples,while the equal population of males and females were found in toxic range.In male children,more samples were in sub-therapeutic levels as compared to infants,adult,and elderly males.In female infants,more samples were in sub-therapeutic levels as compared to children,adult and the elderly.Conclusion:The outcomes of the current research work exposed that despite the majority of samples in the therapeutic range there was an unfavorable clinical response.An increased number of female,male children and female infant samples within sub-therapeutic range may be due to non-compliance or improper dosages which results in an unfavorable clinical response.Female,male children and female infant may require a higher dosage to achieve the maximum clinical response.However,this requires further investigation.Through these results,it can be concluded that there is a poor relationship between valproic acid plasma concentration and clinical response.PART 4:The impact of Antiepileptic Drugs on Vitamin Levels in Epileptic PatientsBackground:Several studies reported that treatment with antiepileptic drugs alters the vitamins levels in epileptic patients which may mediate the toxicity of antiepileptics.Conversely,numerous studies have stated that vitamin levels are not affected by the antiepileptic drugs.With no clear conclusions on the impact of antiepileptics on serum levels of vitamins,there is a need for further clinical study in order to ascertain the impact of old and newer antiepileptics on serum levels of vitamins in epileptic patients,thus accomplishing a suitable usage of vitamin supplementation.Many reports have stated the antiseizure effects of some vitamins.Alteration in normal vitamin levels may negatively affect overall health.Objective:The intention of the present research is to confirm the hypothesis of whether or not vitamin levels are altered with antiepileptic drugs.The study also aims to reveal which vitamin levels are altered,the vitamin levels affected by gender and the type and number of antiepileptics used.Methods:This research work was piloted in collaboration with the Neurology Department in Qilu Hospital of Shandong University.A total of 63 serum samples of epileptic patients receiving antiepileptics as monotherapy or polytherapy were requested for analysis of nine vitamin serum levels.A total of nine vitamins from epileptic patients receiving antiepileptic drugs were analyzed.The serum results of nine vitamins(A,B1,B2,B6,B9,B12,C,D and E)of epileptic patients were separately compiled and evaluated with SPSS.The analysis of all vitamins was performed in our lab using the same electrochemical assay.Results:It was alarmingly found that serum levels of vitamin D were particularly very low in almost all(90%)epileptic patients in this study.Notably,serum levels of vitamin C and vitamin B1 were also below reference range in 72%and 46%epileptic patients,respectively.The remaining vitamins were almost in reference range in most of the patients.In our study,the mean and frequency of vitamin D,C,and B1 levels did not vary too much among different gender groups.The patients receiving newer antiepileptic drugs displayed slightly increased vitamin D serum levels in comparison to the patients receiving older antiepileptic drugs.We found low vitamin D,C and B1 serum levels in patients who were on monotherapy as in comparison with patients on polytherapy.Conclusion:The most significant and surprising finding of this study revealed that serum vitamin D levels,in particular,were very low in almost all patients and in some patients vitamin B1 serum levels were also below the reference range.More importantly,it is also reported here that vitamin C serum levels were below reference range as well in the majority of these Chinese epileptic patients.It is recommended that all these vitamins should be regularly monitored in addition to antiepileptic drugs monitoring.It is also recommended that epileptic patients with low serum levels of these vitamins should be prescribed vitamin supplements with antiepileptic drugs in order to effectively achieve freedom from seizures.Further clinical trials are required for further investigations.Conclusion of all four partsThe present research explores the novel chromatographic and modern methods for quantification of antiepileptics and vitamin levels in epileptic patients.The present research will be helpful for clinicians and patients in improving the outcome of fatal epilepsy disease and controlling the seizures more effectively.The present research is divided into four main parts.PART 1:Development and Validation of Novel Methods for Antiepileptic Drugs1.Simple,fast,reliable,highly sensitive,cost-effective and novel liquid chromatography/mass spectrometry(LC/MS)methods with simple extraction procedures,less plasma volume,shorter run time and low limit of quantitation for the determination of carbamazepine and phenytoin in human plasma were developed and validated.2.Simple,fast,reliable,highly sensitive,cost-effective and novel high performance liquid chromatography(HPLC)methods with simple extraction procedures,less plasma volume,shorter run time and low limit of quantitation for the determination of lamotrigine and levetiracetam in human plasma were developed and validated.3.These methods were successfully utilized in Therapeutic Drug Monitoring of epileptic patients.These assay methods can also be applied in other clinical applications such as pharmacokinetics,toxicokinetics and bioequivalence studies.4.The stated four chromatographic methods have the following advantages.● 8These methods are simple,fast,precise and highly sensitive and less plasma volun is required.● These methods are sensitive enough even for quantifying very low concentrations.● Sample preparations are simple,very easy and cost effective and have reduced riskanalytical errors.Furthermore,the sample preparation procedures of our develop techniques are faster,easily manageable,less pollutant and give better recove values than complex liquid-liquid extraction procedures and expensive solid-pha extraction procedures described in the literature.● The analysis time is shorter than described methods in the literature.Due to this,large number of patient samples can be quantified in a shorter time and this is a gre advantage in TDM.● The quantitation range of the described methods is broader than reported methods.● The specificity,recovery,linearity,stability and accuracy and precision resultsabove stated methods were ideal and within acceptable limits of Internation Conference on Harmonisation guidelines.PART 2:Evaluation of Correlation of Developed and Validated LC/MS MethodsCarbamazepine and Phenytoin with Modern Techniques(Enzyme-multiplie Immunoassay Technique EMIT)in TDM1.Excellent correlation(R2= 0.971)was observed between LC/MS results and resultsEMIT in TDM of Carbamazepine.2.Decent correlation(R2= 0.921)was noticed between LC/MS results and results of EMI in TDM of Phenytoin.3.LC/MS therapeutic drug monitoring results were accurate and trustworthy.4.EMIT is quicker,inexpensive,requires less labor and time and can also be suitably applied in routine TDM of carbamazepine and phenytoin.PART 3:Assessment of the Relationship between Plasma Concentrations of Carbamazepine,Phenytoin and Valproic Acid with Clinical Response,Safety and Toxicity in Different Age and Gender Groups of Chinese Epileptic Patients with the Applications of TDM1.Majority of patients who were using phenytoin,and nearly half of the patients who were using carbamazepine and valproic acid,had plasma concentration results out of reference range and unfavorable clinical responses were noticed in these patients.2.The difference in plasma concentration of carbamazepine,phenytoin and valproic acid was notably altered in gender and various age groups.Compared to males and compared to adults and elderly,females and children patient samples had an increased number of samples in out of reference range.We speculate that uncontrolled seizures or toxicity and unfavorable clinical response in most of these patients may be most probably because of out of therapeutic range.The main reasons for out of therapeutic range in these patients may be poor compliance,underdose,overdose or improper self-dosages taken by patients themselves resulting in the plasma concentration is out of the reference range and unfavorable clinical response.Other factors such as genetic factors,variations in genetic polymorphism,intra and inter-individual variations in pharmacokinetics parameters,pathological conditions,pharmacokinetics interactions and special conditions such as pregnancy and age-related body response to the drugs may also cause the variations in plasma concentration and therapeutic response.This may also be due to metabolic differences that occur in different age groups and genders.We speculate that pregnancy may be a contributing factor which can cause the differences in weight,changing plasma constituents,hemodynamic variations,hormonal factors,and contribution of the fetoplacental unit to drug distribution and disposition resulting in a decrease in total concentration of the above mentioned old generation antiepileptics.Children and infants are unique groups because of the rapid metabolic rate and rapid elimination time and larger volume of distribution values and females also have rapid metabolic rate and rapid elimination during pregnancy.These factors in children,infants and females may be also responsible for sub-therapeutic levels.However,all these factors require further vigilant evaluation3.Careful attention must be applied to specific gender and particular age group on the individual basis,in order to facilitate the modification of doses and develop the best approach to treatment and to obtain the desired clinical response.4.A positive correlation between the clinical response and plasma concentration of carbamazepine and phenytoin and a negative correlation between the clinical response and plasma concentration of valproic acid was observed.However,it needs further evaluation.PART 4:The impact of Antiepileptic Drugs on Vitamin Levels in Epileptic Patients1.The most significant and surprising finding of vitamin levels in Chinese epileptic patients was that almost all patients receiving antiepileptics had severely low levels of vitamin D;vitamin C and vitamin B1 that were also below the reference range in the majority of these patients.2.Interestingly vitamin D levels vary between older and newer antiepileptic drugs and no noteworthy difference in serum vitamin D levels was found among different gender groups.The patients receiving newer antiepileptic drugs displayed a slightly increased serum vitamin D level in comparison to the patients receiving older antiepileptic drugs.3.Patients who were on monotherapy had decreased serum levels of vitamin D,C,and B1 as compared to patients on polytherapy.4.These vitamins work as neuroprotective agents.Keeping in view of the current situation of Chinese epileptic patients,it is proposed that these vitamins should be regularly monitored and avoiding of vitamin D,C and B1 deficiency might be an economical and easier way to reduce the incidence or harshness of epileptic seizures in Chinese epileptic population.5.It is also anticipated that epileptic patients with low serum levels of these vitamins may be prescribed vitamins supplementations with antiepileptic drugs in order to effectively achieve freedom from seizures.Further clinical trials and investigations are required. |
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