Phenytoin Drug Research Articles

The Phenytoin Ataxia Enigma Unveiled ''A Case Report''.

Background: Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Case: Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. Conclusion: In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.

Drug Induced Gingival Enlargement: Non-Surgical Management

Gingival overgrowth was a side effect of several different drug classes, including anticonvulsants, immunosuppressants, and calcium channel blockers. Extracellular collagenous matrix components accumulate together with varying degrees of inflammation to describe it. The anti-epileptic phenytoin is one of the main medications linked to gingival overgrowth. It affects gingival tissues by changing the metabolism of extracellular matrix. This paper aims to present a case report on non-surgical management of phenytoin drug induced gingival enlargement.

Phenytoin regulates osteogenic differentiation of human bone marrow stem cells by PI3K/Akt pathway

BackgroundWe mainly studied the mechanism by which phenytoin promotes osteogenic differentiation of human jawbone marrow stem cells. MethodsBone marrow stem cells were extracted from jaw bone tissue debris obtained from 5 subjects undergoing implant restoration. Osteogenic and adipogenic experiments proved cells stemness, and the expression of ALP, RUNX2, and OSX were detected by qPCR and Western blot. High-throughput sequencing was used to extract differentially expressed genes, the network database predicted phenytoin drug targets, GO and KEGG enrichment combined with PPI network diagram to analyze the osteogenesis mechanism. ResultsCalcium nodules and lipid droplet formation were observed in osteogenic and adipogenic experiments. The concentration of phenytoin within 100 mg/L does not produce cytotoxicity. The results of PCR and WB indicated that 50 mg/L phenytoin significantly promoted the expression of ALP and RUNX2, and 25 mg/L phenytoin significantly promoted the expression of OSX. The results of network pharmacology suggest that phenytoin promotes bone formation by up-regulating FGFR2, S1PR1, TGFB3, VCAN core proteins and activating PI3K/Akt pathway. ConclusionsPhenytoin activated the PI3K/Akt pathway to regulate the osteogenic differentiation of human jawbone marrow stem cells. https://data.mendeley.com/datasets/t3xstktt93/1.

Phenytoin drug detection study through the B24N24 and Al24N24 nano-clusters in gas and solvent phase: DFT, TD-DFT, and thermodynamic study

Chemical sensors could pioneer great utilities in point-of-care diagnostic medical devices. Therefore, the interaction of the B24N24 and Al24N24 nano-clusters with phenytoin was theoretically studied to explore a potential chemical sensor. All calculations were performed using the B3LYP-D method in the gas and solution phases. The absorption energies were -12.54 and -35.36 kcal mol-1 for B24N24 and Al24N24, in the most stable orientations, respectively. Thermodynamic investigations were shown the interaction of PHT with the nano-clusters is spontaneous and exothermic. Electrical conductivity after the adsorption process was changed to -23.94% and -6.81% in the B24N24 and Al24N24, respectively. Thus, it is clear that the B24N24 nano-cluster demonstrated a significant alteration in the electrical conductivity, and these changes could be considered the signal for the detection of PHT. Further, the B24N24 nano-cluster had a practical short recovery time of 1.52 ×10-5 s. Furthermore, solvent calculations indicated that the nano-clusters also could be used in biological samples. UV-vis calculation showed after the interaction of PHT with the B24N24 spectrum shifted significantly to the higher wavelength region (red shift). The concentration calculations showed a concentration-independent sensor response in the B24N24 nano-cluster. Thus, it can be concluded that the B24N24 nano-cluster is an appropriate candidate for PHT detection and this nano-cluster can be used in sensor devices.

Development of advanced model for understanding the behavior of drug solubility in green solvents: Machine learning modeling for small-molecule API solubility prediction

Determination of small-molecule API (Active Pharmaceutical Ingredient) solubility in solvents is of great importance for drug development in pharmaceutical industry. This study uses machine learning algorithms to predict the solubility of phenytoin drug and density of the solvent at different pressure and temperature. In fact, the solubility of drug (y) and the density of supercritical CO2 (Sc-CO2) were investigated as functions of temperature (T) and pressure (P). Three regression models, namely Gaussian Process Regression (GPR), Gamma Regression (GR), and K-nearest neighbor (KNN) were employed to predict the output variables. To optimize the performance of these models, the Directional Bat Algorithm (dBA) was utilized for hyper-parameter tuning. The outputs demonstrated the accuracy of the developed models in predicting the Sc-CO2 density and solubility of phenytoin. Among the models, GPR exhibited the highest accuracy for both outputs, achieving an R2 value of 0.99 for the solvent density and 0.999 for the solubility. The root mean square error (RMSE) for Sc-CO2 density was approximately 18.37, with an average absolute relative deviation percentage (AARD%) of 4.07% and a maximum error of 37.42. For solubility, the RMSE was approximately 0.087, with an AARD% of 2.29% and a maximum error of 0.150.

Polymer stabilized, phenytoin-loaded nanomicelles as promising nanocarriers: In silico and in vitro evaluations

Many drugs currently used in clinics to treat different diseases show low solubilities in aqueous solutions and must be then administered with the aid of organic solvents within the designed formulations leading to harmful health effects. For such reason, drug delivery using nanocarriers appears as an excellent alternative since it improves the solubilization and controlled release of many different pharmaceuticals, favoring the decrease of the overall administered therapeutic doses and by diminishing the risk of potential associated adverse side effects. Among the different types of nanocarriers, those based on polymeric micelles are an excellent option since the polymer structure and composition may be tuned in order to regulate the characteristics and properties of the resulting nanoassemblies to maximize drug solubilization and release profiles. For this reason, in this paper a drug delivery nanosystem based on oil-in-water polymeric-based microemulsion used to load the anti-epileptic phenytoin drug (PHT) was developed in the oily phase. Two different biocompatible polymers were evaluated to form the nanomicelles and maximize encapsulation efficiencies and colloidal stability: The amphiphilic triblock copolymer Pluronic F127, which poses the ability to cross the blood brain barrier (BBB), and the natural lipophilic lignin, which bears antipathogenic properties. Density functional theory (DFT) calculations were performed with the 6-31G(d) basis set to elucidate the interactions of PHT with F127 and lignin monomers. Simulation data showed that hydrogen bonding (HB) interactions between PHT, F127 and lignin are the predominant force to allow for drug solubilization and stability. Atoms in molecules (AIM) and natural bond orbital (NBO) analyses were performed to evaluate the strength of such HB. and their drug encapsulation efficiency, release profiles, and antibacterial susceptibility were determined. Moreover, the cytotoxicity of the developed nanoformulations together with a morphological examination of PC12 and NIH cells after drug-loaded nanocarrier administration and subsequent uptake were also investigated. In this manner, the obtained nanocarriers were also characterized by dynamic light scattering (DLS) and zeta potential, showing a nanometer size (between ca. 16 and 22 nm) and surface negative charge. PHT loading into F127 and lignin nanomicelles were ca. 96.7 ± 1.5% and 68.2 ± 3.5%, respectively, and the drug release profile kinetics of F127/PHT-loaded nanomicelles was rather slower compared to that of lignin/PHT-loaded ones. On the other hand, in vitro cytotoxicity data confirmed the lack of any significant cytotoxicity of PHT-loaded nanomicelles in both NIH/3T3 and PC12 cell lines, but a slightly higher cell viability and well-preserved cell morphology was observed for PC12 cells compared to NIH/3T3 ones. After culturing in chocolate blood agar medium inoculated with F127/PHT-loaded and lignin/ PHT-loaded nanomicelles, pathogenic bacteria did not grow despite confirming certain antimicrobial character of the encapsulated drug. Hence, thanks to their excellent encapsulation and biocompatibility properties, these nanocarriers appear as an excellent option to configure new drug delivery nanocarriers of hydrophobic drugs.

Investigation on the potential application of some metal oxide nanoclusters in the detection of phenytoin in gas and solvent phases through density functional theory calculations

To explore an appropriate sensor for the phenytoin (PHT) drug, metal oxide nanoclusters (Zn12O12, Mg12O12, and Be12O12) were used to adsorb the PHT utilizing the density functional theory calculations. After the interaction of PHT with nanoclusters, the adsorption energies were obtained to be − 60.17, −45.57, and –32.75 kcal mol−1, respectively. Thermodynamic parameters indicated that the adsorption of PHT on the nanoclusters is exothermic and spontaneous. After the adsorption process, electrical conductivity changed to 1.18, −8.68 %, and − 26.65 % in the Zn12O12, Mg12O12, and Be12O12, respectively. Thus, the electrical conductivity values indicated that the Be12O12 nanocluster has changed after adsorption, and this change can be considered the signal for the detection of PHT. Furthermore, Be12O12 indicated an ideal recovery time for PHT desorption from the nanocluster. Solvent phase calculations indicated that the nanoclusters also could be used in biological samples. UV–vis calculation showed that after the adsorption of PHT on the Be12O12, the spectrum shifted to a higher wavelength (red shift). Thus, it can be concluded that the Be12O12 nanocluster is an appropriate candidate for PHT detection.

Adsorption properties of B12N12, AlB11N12, and GaB11N12 nanostructure in gas and solvent phase for phenytoin detecting: A DFT study

• Interaction of phenytoin drug with B 12 N 12 , AlB 11 N 12 , and GaB 11 N 12 nanoclusters was investigated using DFT and TD-DFT calculations. • Adsorption of phenytoin on B 12 N 12 and GaB 11 N 12 changes the energy gap. • The recovery time of B 12 N 12 nanocluster being approximately equal to 0.03 s. • B 12 N 12 nanocluster can be a promising sensor for phenytoin drug. The adsorption properties of phenytoin (PHT) on B 12 N 12 , AlB 11 N 12 , and GaB 11 N 12 nanoclusters were theoretically investigated to find a suitable sensor. All calculations were performed using the B3LYP-D density functional theory in the gas and solution phases. The absorption energy was -22.45, -55.67, and -53.33 kcal mol -1 for B 12 N 12 , AlB 11 N 12 , and GaB 11 N 12 in their most stable configurations, respectively. After PHT adsorption on nanoclusters, their electrical conductivity changes occurred -28.19%, 7.73%, and 27.19 % for the B 12 N 12 , AlB 11 N 12 , and GaB 11 N 12 , respectively. Thus, it is clear that the B 12 N 12 and GaB 11 N 12 nanoclusters indicated a considerable change in electrical conductivity. On the other hand, the recovery time calculation based on transition theory confirmed that only the pristine B 12 N 12 showed a short recovery time of 0.03 s, demonstrating that PHT adsorption on that is reversible and more favorable. The solution phase calculations showed that interacted complexes are stable in water and more sensitive and reactive toward the PHT molecule in the water phase. The UV-vis spectroscopy result revealed that the PHT/B 12 N 12 complex exhibits a shift to higher wavelength (lower energies) regions. Therefore, it is concluded that the B 12 N 12 nanocluster can be used as a suitable detector of phenytoin.

Development and Characterization of Acetazolamide Nanoemulsion for Effective Ocular Delivery

Nanoemulsion has the potential of releasing the drug continuously, and they may easily permeate via the intense layers of the eye structure due to nano-size droplets, which makes nanoemulsion an effective drug delivery system for ocular delivery. The objective of our work was to prepare a nanoemulsion of acetazolamide for glaucoma treatment with enhanced efficacy as well as for continuous effect. Based on different compositions of oil (Olive Oil), surfactants (Tween-20), and co- surfactants (Transcutol P), forty-five test mixtures were made, water titration technique was employed for preparing the pseudo-ternary-phase diagrams. On the basis of these phase diagrams, twenty-five acetazolamide loaded nanoemulsion were formulated and examined for their nanosized droplets, PDI, zeta potential, viscosity, pH, transmittance and in-vitro drug release. The formulated nanoemulsion showed all the properties within the desired range i.e., droplet size (15.6 to 21.18), zeta potential (-15.5 to- 24.71), PDI (0.140 to 0.361), viscosity (3.234 ± 0.063to 5.174 ± 0.023cps), pH (6.922 ± 0.026to 7.033 ± 0.012), RI (1.379 ± 0.007 to 1.404 ± 0.006) and % transmittance was found (94.96± 0.6% to 96.68± 0.6%) and also the release rate of acetazolamide from nanoemulsion was found very good i.e., 81.59± 1.04% to 92.46± 0.33% after 24 hrs. The top four formulations having good drug release were selected for further evaluation of droplet sizes and which also fall in the nano range (15.68 to 21.18 nm). The study showed that it is possible to develop nanoemulsion of phenytoin drug, and the in-vitro drug release study showed that the prepared nanoemulsion had good bioavailability, sustained release and ability to target eye as an effective ocular delivery system.

Use of Saliva as an Alternative Matrix to Serum/Plasma for Therapeutic Drug Monitoring Using Reverse-Phase HPLC

This study was conducted to examine and verify the use of saliva as an alternative matrix for monitoring phenytoin drug levels in patients with epilepsy. Drug concentrations are measured to evaluate whether a suitable drug level has been achieved to minimize the risk for toxicity, inadequate efficacy, or therapy resistance and compliance issues. Quantitative analysis was performed by using reverse-phase HPLC after sample pretreatment with acetonitrile. Seventy-eight patients who met the inclusion/exclusion criteria were examined in this study. Trough concentrations of both saliva and serum were taken at steady state. Of the 78 patients enrolled, only 11 (14.1%) had normal levels. Twenty-eight patients (35.9%) had subtherapeutic levels, and 39 (50%) had toxic levels. Simultaneously, salivary phenytoin levels were analyzed; only 13 patients (17.3%) had therapeutic levels, 25 patients (33.3%) had subtherapeutic levels, and 37 (49.3%) had toxic levels. Among the study population, most of the patients were aged 31 to 40 years (25.6%) followed by the age group 21 to 30 years (19.2%). The lowest percentage of patients were in the age groups 71 to 80 years and >80 years (1.3%) each. This study found a statistically significant relationship between free serum and salivary phenytoin levels (P < 0.001). A very weak and insignificant correlation was observed between serum/salivary phenytoin levels and sex/age of the study population. The results of the present study support the use of saliva as an alternative to serum/plasma for monitoring phenytoin therapy. The free concentration of a drug represents the freely diffusible drug fraction, which is the therapeutically active form. Accordingly, the free drug concentration correlates to clinical efficacy and drug toxicity better than total concentration.

Development and Evaluation of Nanoemulsions for Phenytoin Drug Loading

Aims: To understand about the nanoemulsion types and the process formation of spontaneous emulsification method by phase inversion. Then to test the different combinations of Oil, Surfactants and Co-surfactants for formation of suitable nanoemulsions for phenytoin drug loading.&#x0D; Study Design: Spontaneous emulsification method by phase inversion used to form the nanoemulsions.&#x0D; Place and Duration of Study: Department of Pharmaceutical Sciences, Kumaun University, Nainital, Uttarakhand, India.&#x0D; Methodology: Phenytoin is a widely used drug in anticonvulsants class for epilepsy which comes under BCS Class II of drug category. Phenytoin has high permeability property but it also shows low solubility property which makes it difficult to absorb from GI tract hence make a poor penetration into the brain to target disease in the CNS. To overcome the situation of poor delivery of phenytoin, the requirement of nanoparticulate drug delivery as an innovative and effective drug delivery system from nose to brain raised. The objective of our study was to find the best combination of oil and Smix (surfactant and co-surfactant mixture) to form o/w (Oil in Water) nanoemulsions suitable for loading phenytoin drug using spontaneous emulsification method for brain targeting.&#x0D; Results: Based on different compositions of oil (sunflower), surfactants (Tween-20), and co-surfactants (Transcutol P), forty-five test mixtures were made, water titration technique was employed for preparing the pseudo-ternary-phase diagrams. On the basis of these phase diagrams twenty-five phenytoin loaded nanoemulsions were formulated and further examined. After physicochemical characterization of these formulations the viscosity, pH, RI and % transmittance was found (6.149 ± 0.084 to 9.114 ± 0.027), (6.546 ± 0.018 to 6.656 ± 0.017), (1.395 ± 0.003 to 1.41 ± 0.005) and (94.53 ± 1.4% to 95.58 ± 1.2%) respectively. The release rate of phenytoin was found very satisfactory i.e., 98.51 ± 0.25 % to 99.82 ± 0.28 % after 24 hrs. The four formulations showed best release rate had further taken for particle size analysis. The particle size analysis showed that all the properties were in the desired range i.e., droplet size (18.9 to 21.9), zeta potential (-12.4 to -28.8), PDI (0.334 to 0.363). The study shows that the phenytoin loaded nanoemulsion is possible to make by water titration method and shall have a good drug release rate.&#x0D; Conclusion: The nanoemulsion formulations passed through stress testing had also showed good release rate of phenytoin. Also, the other parameters like viscosity, pH, RI and percentage transmittance were in a quit satisfactory range to proceed further with these formulations. The particle size analysis confirms the formation of nanoemultions which had very good drug release rates.

Study of Phenytoin Effect on the genes involved in glucose and lipid metabolism expression in liver: A mouse model study

Phenytoin as an anti-seizure medication, is useful for the prevention of tonic-clonic seizures and focal seizures. In this study we focused on the probable effects of Phenytoin drug on gene expression profile of liver related to lipid metabolism balance in mouse as a model. In this study, a group including 7 male mice of BALB/c were treated with phenytoin 3–5 mg/kg/day orally and a group including 7 male mice of BALB/c were took standard food. Liver tissue samples were isolated. Total RNA was extracted and cDNA was synthesized. Expression of Akt1 , Leptin, Adipoq and GLUT4 genes was measured using Real-time RT-PCR method. Results showed an increase about 15 and 3 fold changes in Akt1 and Adipoq gene expression respectively in treatment group compare to control mice. Also, we detected decreasing in Leptin and GLUT4 genes expression in the mice treated with phenytoin drug. Several studies indicated that phenytoin can promote hyperglycemia in human and animal. We proposed here that this effects may resulted from an interference between the phenytoin drug and gene expression profile in liver. Decreasing of leptin level here may be a result of glucose level elevation in blood that can induce a satiety situation result in decrease of leptin production. It may that Akt1 gene expression is increased to compensate the low level of GLUT4 protein. We concluded that phenytoin is a relatively high-risk antiepileptic drug for obesity and metabolic syndrome, but more studies are needed.

Correlation between serum and salivary phenytoin drug metabolite levels to phenytoin influenced gingival overgrowth in adult male subjects. A prospective cohort study

BackgroundTo correlate serum and salivary phenytoin drug metabolite levels in males to phenytoin influenced gingival overgrowth (PIGO). MethodsThirty male patients who are to start with oral phenytoin therapy were recruited. Plaque index (PI), Gingival index (GI), and Oral hygiene index (OHI) were recorded. Basic periodontal therapy was performed. Patients were followed up at 3, 6, 9 and 12 months intervals. Based on the gingival status they were divided in to two groups; Group1 (responders) and Group 2 (non responders). Serum and Salivary samples were analyzed for the drug metabolite levels spectophotometrically. ResultsThe mean values of phenytoin drug metabolite levels in serum of group 1 and group 2 subjects were 14.5±2.6μg/ml and 14.2±1.7μg/ml respectively, with p value of 0.66. The corresponding mean values of phenytoin drug metabolite levels saliva were 1.42±0.34μg/ml and 1.38±0.37μg/ml with p value of 0.75. Correlation of phenytoin drug metabolite to PI, GI, and OHI in both the groups did not show any statistical significance. (R values ranging from −0.229 to 0.434). Correlation between the serum and salivary drug metabolites in both the responder and non responder group also did not show any statistically significant relationship. ConclusionNo correlation between the drug concentration in either the serum or saliva can be correlated to PIGO. Whole Saliva could be a useful tool in therapeutic drug monitoring of phenytoin. Clinical relevanceScientific rationale: To assess and compare the drug metabolite levels in serum and saliva of a neurologic condition where therapeutic drug concentration is of key importance to minimize the side effects. Principle finding: Saliva could be as useful as serum in deciding the drug concentration of phenytoin. And PIGO is not related drug concentrations. Practical implication: Monitoring the drug dosage is of paramount importance for the success of antiepileptic therapy as well as control of its side effects. This longitudinal study confirms that saliva could be an effective alternative to serum for monitoring drug dosage of phenytoin.

Assessing the Efficacy of Poly(N-isopropylacrylamide) for Drug Delivery Applications Using Molecular Dynamics Simulations.

All-atom molecular dynamic simulations (AA-MD) are performed for aqueous solutions of hydrophobic drug molecules (phenytoin) with model polymer excipients, namely, (1) N-isopropylacrylamide, (pNIPAAm), (2) pNIPAAm-co-acrylamide (Am), and (3) pNIPAAm-co-dimethylacrylamide (DMA). After validating the force field parameters using the well-known lower critical solution behavior of pNIPAAm, we simulate the polymer-drug complex in water and its behavior at temperatures below (295 K) and above the LCST (310 K). Using radial distribution functions, we find that there is an optimum comonomer molar fraction of around 20-30% DMA at which interaction with phenytoin drug molecules is strongest, consistent with recent experimental findings. The results provide evidence that molecular simulations are able to provide guidance in the optimization of novel polymer excipients for drug release.

Presence of a single nucleotide polymorphism (RS3758581) in a boy with DRESS syndrome

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes rash, hematologic abnormalities, lymphadenopathy, and internal organ involvement. The pathogenesis of DRESS syndrome is partially understood. Various medications have been described as the cause of DRESS syndrome. Phenytoin and allopurinol are the most commonly reported culprit drugs, although more than 50 drugs can induce DRESS syndrome. Members of the cytochrome P450 (CYP) superfamily are the most commonly involved enzymes in metabolism of drugs such as phenytoin. This case report addresses the influence of CYP2C9 genetic polymorphism (a single nucleotide polymorphism) on phenytoin drug metabolism, thereby causing DRESS syndrome.

Study on analysis of the causes for the failure of Antiepileptic treatment in children with seizure disorders in a tertiary centre.

Objective: To study and analyze the causes for the failure of Anti epileptic treatment in children with seizure disorder in relation to age, sex, type of seizure and possible etiology. Design: Prospective observational cross sectional descriptive study. Setting: Children between 1-14 years who are suffering with recurrent seizures who are taking AEDs were taken for the study for a period of 6months (from Jan 2011 to June 2011) who were admitted in emergency and pediatric wards of Institute of Child and Women Health, Niloufer Hospital, Osmania Medical College, Hyderabad. Participants: Over a period of 6 months, 120 children between 1 14years were admitted in the hospital, were included and 3 were excluded because they are lost to follow up. Methods: All children with recurrence of seizures who are admitted pediatric wards and in emergency were constitute the study sample. The factors causing the recurrence of seizures were studied in the preset proforma. A thorough clinical examination of the study sample is done and including the relevant investigations. The data was analyzed statistically by using ODDS Ratio, and Relative Risk ratios, Chi-square test. For all children with seizures EEG and CECT were done. Age below1 year, above 14 years, any episode without antiepileptic treatment and Myoclonic seizures, Cerebral plasy with more than 1 Anti epileptic drug, Neurocutaneous syndrome, Lenox Gestaut syndrome, West syndrome were excluded from the study. Results: This study is comprised of 120 children (76 were male and 44were female) out of which 80(66.67%) children suffered with GTCS, 33(27.5%) suffered with complex partial seizures and remaining 7(5.83%) with atypical febrile seizures. Noncompliance is more common in more than 6 years children than less than 6 years. The p value is 6 years and the odds ratio is 1.69.GTCS type of seizures is more common recurrence in the age of above 6 yrs than below 6 yrs age group. The RR is 1.29in above 6 years. Conclusions: Male children were more commonly get recurrence of seizures (63%). Phenytoin drug users were more likely to get the recurrence of seizures.

Quick and Simple Formation of Charge Transfer Complexes of Brain and Nerves Phenytoin Drug with Different π–acceptors: Chemical and Biological Studies

Quick and Simple Formation of Charge Transfer Complexes of Brain and Nerves Phenytoin Drug with Different π–acceptors: Chemical and Biological Studies

Detection of the antiepileptic drug phenytoin using a single free-standing piezoresistive microcantilever for therapeutic drug monitoring

Phenytoin, one of the most widely used antiepileptic drugs, suppresses the abnormal brain activity often seen in seizures. In this study, we report the electrical detection of phenytoin as an antiepileptic medication with a narrow therapeutic dosage range to which therapeutic drug monitoring (TDM) is applied. The measurement technique used an electrical detection of a piezoresistive microcantilever biosensor. This label-free, electrically measured microcantilever can be miniaturized in order to be portable for point-of-care, personal diagnosis or for personalized therapeutic drug monitoring. The miniaturized piezoresistive microcantilever was fabricated by micro-electro-mechanical system processes, and was integrated into a microfluidic channel with a system for label-free detection. The microcantilever biosensor was approved for the detection of phenytoin in solutions of deionized water and 100% fetal bovine serum. A linear profile in a drug-concentration range of 10–80μg/mL was detected, with the signal resolution being about 0.005Ω. The concentration sensitivity was 2.94×10−6(μg/mL)−1. The binding affinity (KD) was calculated to be 58μg/mL. The results of the present piezoresistive microcantilever biosensors showed a solid correlation of phenytoin drug detection with that in the clinically used fluorescence polarization immunoassay (FPIA).

Cytochrome P450 2C9 gene polymorphism in phenytoin induced gingival enlargement: A case report

Gingival enlargement comprises any clinical condition in which an increase in the size of the gingiva is observed. Among the drugs that induce gingival enlargement, the antiepileptic agent phenytoin has been widely related to this condition. The Cytochrome P450(CYP) superfamily is the most commonly involved enzymes in metabolism of drugs. Common coding region CYP variants that affects drug elimination and response has been studied in great detail. Pharmacogenetic influences on drug metabolism have been widely reviewed and gene polymorphism of cytochrome P450 2C9 appeared to be responsible for much of the interindividual variability on drug elimination. Genetic variation in the CYP2C9 gene can affect metabolism, leading to altered phenotypes. Individuals with poor metaboliser alleles of CYP2C9 gene were shown to have a reduced metabolism of phenytoin compared with wild-type alleles. Thus identification of patients genotype prior to anti-epileptic drug administration could potentially prevent higher serum drug concentrations leading to adverse side effects such as gingival enlargement. This case report addresses the influence of CYP2C9 genetic polymorphism on Phenytoin drug metabolism thereby causing gingival enlargement.

Synthesis and anticonvulsant activity of a new series of 1,4-dihydropyridine derivatives

A series of 1,4-dihydropyridine derivatives (1a–g) were prepared from three compounds condensation of Hantzsch synthesis. A new series of 2,2’-{[4-(aryl)-2,6-dimethyl-1,4-dihydropyridine-3,5-diyl]dicarbonyl}dihydrazinecarbothioamide (2a-g) were prepared from compounds diethyl 4-(aryl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1a-g) reacted with thiosemicarbazide to give the corresponding compounds (2a-g) by hydrazinolysis method. The synthesized compounds were confirmed by IR, 1HNMR, 13CNMR, mass spectral and elemental analyses. The newly synthesized compounds (2a-g) were screened for anticonvulsant activity against in swiss albino rat. The test was evaluated by maximal electrode induced convulsion method. Synthesized compounds were used two (50 and 100 mg/kg) concentrations. Compounds (1a-g) were inactive while compounds (2a-g) have moderate anti-convulsant activity compared with standard phenytoin drug. The compound 2,2’-{[4-(furan-2-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-diyl]dicarbonyl} dihydrazinecarbothioamide (2a) has highly active compared with other compound (2b-2g).