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Aim To explore the important role of HDAC5 in P-gp expression in rats in high-altitude low oxygen environment and its effect on phenytoin sodium pharmacokinetics. Methods Wistar rats were transported to Batang, Yushu, Qinghai, at an altitude of 4010 m, with 6 rats in each group, divided into 1 d and 3 d groups. Different groups were given phenytoin, phenytoin combined with hypericin, and phenytoin combined with verapamil. Plasma and liver tissues were collected at different time after taking the drug in the plateau area. The concentration of phenytoin sodium in plasma was determined by UFLC-MS method. Changes in protein expression were detected by Western blot. Results The results of UFLC-MS showed that the AUC
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Background: Epilepsy is a chronic disorder characterised by recurrent seizures/convulsions that affects people of all ages. Phenytoin sodium is an effective, cheaper, most commonly used first line drug for the treatment of epilepsy. As a result of sure encounter with various painful inflammatory conditions like chronic arthritis at some point of time the co administration of analgesics becomes inevitable in epileptic patients. Aceclofenac is a commonly prescribed, moderately COX-2 selective congener of Diclofenac. Because of similarity in some pharmacokinetic properties between Phenytoin sodium and Aceclofenac; the possibility of drug interaction between them is postulated.Methods: In this prospective randomized observational study diagnosed and stabilized patients of epilepsy of either sex of more than 18 years of age were included. Patient taking Phenytoin sodium 100mg BD and prescribed tab Aceclofenac 100mg bd for 7 days. Serum Phenytoin sodium levels were measured before and after administering Aceclofenac. Graph pad Prism software Version 6 used for statistical analysis.Results: At the end of the study, we found statistically significant effect (p = 0.0104) on serum Phenytoin sodium level. However, no statistical difference was found in any of the other parameters i.e., epilepsy outcome parameters and lab parameters - Urine routine microscopy, CBC, LFT, KFT and RBG.Conclusions: Findings in this study forms a platform for future researchers to explore this field of research by designing an interventional study with well scrutinised study population considering all pharmacokinetic parameters.
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Objective To investigate the effect of sodium valproate combined with phenytoin sodium on the epileptiform discharge and cognitive function in patients with refractory epilepsy (RE).Methods A total of 213 patients with RE were selected from February 2011 to February 2015 in the Third Affiliated Hospital of Xinxiang Medical University.The patients were divided into phenytoin sodium group,sodium valproate group and combined treatment group according to the treatment methods,71 cases in each group.The patients in the phenytoin sodium group were treated with phenytoin sodium,the patients in the sodium valproate group were treated with sodium valproate,and the patients in the combined treatment group were treated with phenytoin sodium and sodium valproate.The electroencephalogram and cognitive function score of the patients in the three groups were performed before treatment and six months after treatment,and the therapeutic effect was evaluated.The improvement of electroencephalogram,cognitive function score and clinical effect were compared among the three groups.Results The total effective rate in the combined treatment group,phenytoin sodium group and sodium valproate group was 80.28％ (57/71),60.56％ (43/71) and 59.15％ (42/71) respectively,the total effective rate in the combined treatment group was significandy higher than that in the phenytoin sodium group and sodium valproate group (x2 =8.412,9.596;P ＜ 0.05),but there was no significant difference in the total effective rate between phenytoin sodium group and sodium valproate group (x2 =0.003,P ＞ 0.05).The improvement rate of electroencephalogram in the combined treatment group,phenytoin sodium group and sodium valproate group was 80.28％ (57/71),63.38％ (45/71) and 60.56％ (43/71) respectively,the improvement rate of electroencephalogram in the combined treatment group was significantly higher than that in the phenytoin sodium group and sodium valproate group(x2 =7.520,8.412;P ＜ 0.05),but there was no significant difference in the improvement rate of electroencephalogram between phenytoin sodium group and sodium valproate group (x2 =0.070,P ＞ 0.05).There was no significant difference in the scores of total intelligence quotient,language intelligence quotient and performance intelligence quotient in the three groups before treatment (P ＞ 0.05).The scores of total intelligence quotient,language intelligence quotient and performance intelligence quotient after treatment were significantly higher than those before treatment in the three groups (P ＜0.05).After treatment,the scores of total intelligence quotient,language intelligence quotient and performance intelligence quotient in the combined treatment group were significantly higher than those in the phenytoin sodium group and sodium valproate group(P ＞ 0.05);but there was no significant difference in the scores of total intelligence quotient,language intelligence quotient and performance intelligence quotient between the phenytoin sodium group and sodium valproate group (P ＞ 0.05).Conclusion Phenytoin sodium combined with sodium valproate can effectively control the epileptiform discharge,improve the cognitive function and improve the therapeutic effect in RE patients.
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Background: The non-medical self-administration of memory enhancing drugs is a common practice. Present study was designed to evaluate interactions of two such herbal drugs Memory Plus (MP) and Mentat, with other central nervous system (CNS) active drugs. Methods: Two activities - pentobarbitone sleeping time (PST) and maximal electroshock seizures (MES) were performed using adult albino mice weighing 25-30 g to observe the interactions of the herbal drugs with diazepam and phenytoin sodium, respectively. For each activity, animals were divided into seven groups of six mice each. Group I was a control group receiving 0.2 ml of 1% Tween 80 i.p/0.2 ml saline p.o, Group II, III and IV acute treatment groups; received single dose of herbal (2 mg/kg i.p MP or 200 mg/kg p.o Mentat) CNS-active drugs alone in subeffective doses group II - diazepam 5 mg/kg i.p, Group III PS 15 mg/kg i.p and Group IV - MP/Mentat+diazepam or PS, respectively. Groups V, VI, and VII were subchronic treatment groups, received drugs once daily for 8 days same as acute treatment groups. Sleeping time was measured as the interval between the loss and recovery of righting refl ex and anticonvulsant activity by giving supra maximal shock via ear electrodes using a techno electro convulsiometer. Results: Both MP and Mentat showed potentiation of effect of diazepam and PS in subchronic treatment groups by signifi cantly prolonging PST (p<0.05) and by showing signifi cant percentage protection in MES method (p<0.05) compared to control group. Conclusion: Subchronic administration of MP and Mentat shows significant interaction with diazepam and PS. Further human studies are warranted to confi rm these fi ndings.
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Objective:To establish an HPLC method for the determination of clindamycin phosphate in compound phenytoin sodi-um ge1s. Methods:The HPLC analysis was carried out on a ZORBAX SB-C18 column(250 × 46 mm,5 μm)with 0. 1 mol·L-1 KH2PO4 solution(adjusting pH to 2. 5 with H3PO4 solution)-acetonitrile(75:25)as the mobile phase at the flow rate of 0. 8 ml· min-1 . The detection wavelength was 210 nm,the column temperature was 25℃ and the injection volume was 10μl. Results:The lin-ear range of clindamycin phosphate was 3. 00-18. 00 μg(r=0. 999 5). The average recovery was 101. 11%(RSD=0. 34%,n=6). Conclusion:The method is simple,sensitive and reproducible,and can be used in the determination of clindamycin phosphate in com-pound phenytoin sodium gels.
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To evaluate the efficacy of Magnesium sulphate and Phenytoin sodium regime in the prevention & control of eclamptic fits. This retrospective study was conducted for one year. 197 eclamptic cases were reported of which 147 cases were managed with magnesium sulphate and 47 were managed with Phenytoin sodium regime.There were 197 cases of eclampsia among 12,170 deliveries, incidence being 1.61%. In magnesium sulphate regime, seizures were controlled within 4hrs of therapy in 97.94% patients while it was 80.86% in Phenytoin sodium group. Recurrent convulsions with Magnesium sulphate (4.76%) were less as compared to phenytoin sodium(34.04%)p<0.01. 91.8% of patients in Magnesium sulphate regained their consciousness within 12 hrs of therapy while it was only 70-72% in Phenytoin sodium regime p<0.01.It is therefore inferred that Magnesium Sulphate therapy has proved superior to Phenytoin sodium regime because of minimal CNS depressant action, minimal fits recurrence and better level of consciousness.All the above factors collectively help in reducing maternal mortality and morbidity &improving foetal salvage.
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OBJECTIVE:To study the effect of moxifloxacin on pharmacokinetics of phenytoin sodium in rabbits. METHODS: A total of 10 rabbits were injected with phenytoin sodium (10 mg?kg-1) via the vein in ear edge,with serum samples taken at 10,30,60,120,240,360,and 480 min,respectively for establishing phenytoin sodium alone group. 48 h after the last sampling,the rabbits were given oral moxifloxacin (10 mg?kg-1) for 5 consecutive days;on day 6,the rabbits were injected with phenytoin sodium (10 mg?kg-1) at 2 h after oral administration of moxifloxacin,then serum samples were taken at different time points for establishing combination group of phenytoin sodium and moxifloxacin. The serum concentrations of phenytoin sodium at different time points were determined by UV-spectrophotometry and the pharmacokinetic parameters were computed with 3p97 program. RESULTS: The plasma concentration of phenytoin sodium reduced in the combination group compared with alone group. The AUC in the two groups was (5 836.22?489.13) vs. (4 329.21?344.67) mg?min?L-1 (P0.05). CONCLUSION: The elimination of phenytoin sodium was significantly accelerated by combination with moxifloxacin.
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OBJECTIVE:To discuss the significance of therapeutic drug monitoring(TDM)for rational administration of anti-epileptic drugs and to probe into the cognition of clinic staff on TDM.METHODS:Access database of antiepileptic drugs was established to analyze the TDM data of antiepileptic drugs used from 2001 to 2006.RESULTS:The TDM cases of anti-epileptic drugs increased year by year.The proportions of effective concentration,high blood drug concentration and low blood drug concentration derived from TDM data showed that it is quite necessary to conduct blood drug concentration monitoring.But the lack of individual medication information has hindered the development of patients' individualized medication of anti-epileptic drugs.CONCLUSION:The application of TDM is increasingly widespread;however,the joint efforts of physicians and pharmacists are still needed to ensure individualized medication of anti-epileptic drugs.
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BACKGROUND:Many patients with symptom of recurrent episodic vertigo can neither be diagnosed nor treated. The purpose of this study is to review clinical features of a group of patients with recurrent episodic vertigo that is not defined to specific diagnosis of vertigo and to test the effectiveness of phenytoin sodium in the patients. METHOD & MATERIAL:11 of 32 patients with recurrent vertigo not defined to specific diagnostic category of vertigo who visited dizziness center of a tertiary care university hospital from November 1995 to April 2004 were studied. The patient's charts were reviewed retrospectively. A thorough otolaryngologic and neurotologic evaluation was performed in every case to determine the specific cause of dizziness. Vestibular function test, hearing test, magnetic resonance imaging of brain, electroencephalogram, and 24 hour Holter EKG monitoring were performed in all cases. Consultations to psychiatrist and neurologist were obtained. All patients were treated with phenytoin sodium. RESULT:The results of the vestibular function test, audiogram, MRI of brain, electroencephalogram, 24-hr holter monitoring were normal. Any definitive diagnosis could not be reached to this group. Vertigo was controlled by phenytoin sodium in all 11 cases. CONCLUSION:We report a group of patients with recurrent episodic vertigo that is not defined to any specific diagnosis of vertigo. The vertigo symptom was controlled successfully by phenytoin sodium. This patients were diagnosed as benign episodic vertigo as a separate disease entity.
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Humans , Brain , Diagnosis , Dizziness , Electrocardiography , Electrocardiography, Ambulatory , Electroencephalography , Hearing Tests , Magnetic Resonance Imaging , Phenytoin , Psychiatry , Referral and Consultation , Retrospective Studies , Sodium , Tertiary Healthcare , Vertigo , Vestibular Function TestsABSTRACT
AIM: To establish a HPLC method for determining phenytoin sodium and schisandrin in Compound Valpromide Capsule(Valpromide,phenytoin sodium,Fructus Schisandrae Chinensis, VB_6,etc). METHODS: A Hypersil BDS ODS column was used.The mobile phase was MeOH-0.02 mol/L potassium Dihydrogen Phosphate(60∶40).The detection wavelength was at 254 nm. RESULTS: The linear range of phenytoin sodium was within 4.50 ?g-72.0 ?g(r=1.000 0),The linear range of schisandrin was within 0.024 4 ?g- 0.391 ?g(r=0.999 9).The average recoveries(n=9) were 100.21% and 102.32%,respectively.RSD were 1.3% and 0.5%,respectively. CONCLUSION: The method is simple,reliable,accurate and can be applied to the quality control of the preparation.
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OBJECTIVE:To determine serum concentrations of phenbarbital(PB),phenytoin sodium(PHT),carbamazepine(CBZ)by micellar electrokinetic capillary chromatograph(MEKC).METHODS:The determination was performed on elastic quartz column(37 cm?50 ?m)with barbital as internal standard.The buffer solution consisted of 10 mmol?L-1 phosphate sodium buffer-30 mmol?L-1 SDS sodium(micellar phase)-15% methanol at a constant voltage of 18 kV.The detection wavelength was set at 210 nm.RESULTS:The linear concentration ranges of PB and PHT were 2.5～80 ?g?mL-1,with detective concentration of 0.1 ?g?mL-1;the linear range and detective concentration of CBZ were 1～32 ?g?mL-1 and 0.2 ?g?mL-1,respectively.The average recoveries of the PB,PHT,and CBZ were 99.90%,99.91%,and 99.42%,respectively.CONCLUSION:The method is rapid,simple,accurate,sensitive and reproducible,and suitable for clinical monitoring of drug level and pharmaceutical study.
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OBJECTIVE:To study the effect of ethanol on the pharmacokinetics of phenytoin sodium in rabbits METHODS:The serum concentrations of phenytoin sodium at different points of time were determined by UV-spectrophotometry in eight rabbits after administration of phenytoin sodium(10mg/kg)alone and in combination with ethanol RESULTS:After administration in combination with ethanol,the AUC of phenytoin sodium was significantly decreased from(4 108 64?1 039 98)mg/(min L) to (1 903 65?1 003 40)mg/(min L),Cmax from(29 0?2 94)mg/L to(16 0?5 9)mg/L,T1/2(ke) from(98 45?26 4)min to(82 84?25 5)min;but the apparent distribution volume(Vd)was obviously increased from(0 3 475?0 0 360)L/kg to(0 6 819?0 1 901)L/kg and the clearance rate(CL) from(0 0 026?0 0 008)ml/(kg?min)to(0 0 062?0 0 022)ml/(kg?min) CONCLUSION:The elimination of phenytoin sodium was significantly accelerated after simultaneous administration of ethanol in rabbits