ABSTRACT
An analytical methodology based on an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine (MQD)-silica hybrid monolithic column was developed for the enantioseparation of 9-fluorenylmethoxycarbonyl (FMOC) derivatized amino acids by nano-liquid chromatography. The mo-bile phase was optimized including the apparent pH, content of ACN, and concentration of the buffer to obtain a satisfactory enantioresolution performance. 27 FMOC derivatized amino acids including 19 protein and 8 non-protein amino acids were tested, and 19 out of them were enantiomerically discriminated obtaining baseline separation for 11 of them. Analytical characteristics of the method were evaluated for norvaline and tryptophan in terms of linearity, precision, accuracy, limits of detection (LOD) and quantitation (LOQ) showing good performance to be applied to the enantiomeric determination of these amino acids in dietary supplements. LOD and LOQ values were 9.3 and 31μM for norvaline en-antiomers and 7.5 and 25μM for tryptophan enantiomers, respectively. The contents of D-norvaline and D-tryptophan were below their respective LODs in all the analyzed samples. Quantitation of L-tryptophan and L-norvaline showed good agreement with the labeled contents except for one sample which did not show presence of L-norvaline, contrary to the label indication.
ABSTRACT
Nuedexta (dextromethorphan and quinidine) is an Food and Drug Administration approved medication for pseudobulbar affect. Interestingly, this drug was recently reported to improve speech, swallowing, and the ability to handle oral secretions along with emotional lability in amyotrophic lateral sclerosis (ALS) patients with bulbar symptoms. We report a Korean ALS patient whose bulbar function improved after administering Nuedexta for 6 months, extending therapeutic choice of approach in treating ALS patients.
Subject(s)
Humans , Amyotrophic Lateral Sclerosis , Deglutition , Dextromethorphan , Quinidine , United States Food and Drug AdministrationABSTRACT
Background: Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with Class Ia activity. The present study was aimed at analyzing the bioequivalence of the proposed generic product Quinidine Gluconate 324mg Extended Release Tablets with the marketed product of Sun pharmaceuticals, USA.Methods: The design was an open, longitudinal, randomized, comparative study of two formulations in single dose of 324 mg, with a 5 days washout in between doses. The study was conducted in 12 healthy adult male and female Brazilian volunteers under fed conditions in Azidus Brasil, Valinhos, Brazil. Blood samples were collected post dose up to 36 hours for pharmacokinetic analysis and safety evaluation was done by assessing the adverse events and laboratory tests. A validated LC-MS/MS method was used to determine the plasma concentrations of Quinidine. Bioequivalence between the products was established by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-? values for the proposed generic product and marketed product.Results: The 90% confidence intervals found for the relation Test/Reference, were Cmax 80.78% to 109.07%, AUC0-t 86.04% to 104.24% and AUC0-? 86.25% to 104.71%. There were no clinically relevant changes in the vital parameters and the QT, QTc were not adversely affected and both the drug products were found to be safe and tolerable at the given strength.Conclusions: According to FDA´s guidelines for Bioequivalence research, the confidence intervals for Cmax, AUC0-t and AUC0-? ranged between 80.00-125.00%. The above limits obtained were within the accepted bio-equivalence limits.
ABSTRACT
Objective@#To study the mutational characteristics of KCNT1 and its clinical features in children with early-onset epileptic encephalopathy.@*Methods@#Retrospective analysis of clinical data of 175 children with early onset epilepsy from the Department of Pediatrics at Peking University First Hospital from January 2012 to December 2017. Gene-based analysis was performed on children with targeted capture second-generation sequencing and the source of mutations was verified by PCR-Sanger. The clinical features of children with KCNT1 mutation were summarized.@*Results@#In 175 infants with early-onset epileptic encephalopathy, 6 children were found to have KCNT1 mutations, all of which were new mutations with an overall mutation rate of 3.4% (6/175). All the mutations were missense mutations. The age of onset was from 2 days to 32 days. Five children were diagnosed with epilepsy of infancy with migrating focal seizure, one case was diagnosed with epilepsy, focal seizures, focal seizures with generalization. A total of 6 children were treated with multi-antiepileptic drugs. The disease in 4 patients were partially controlled, while in 2 patients, the disease was not significantly alleviated. One patient died of "severe pneumonia" at one year and 4 months of age. Then, four cases were treated with quinidine. The seizure frequency had no change in 3 cases, the frequency decreased and then relapsed in 1 case. The case once ketogenic diet and failed. Ketogenic diet treatment was applied to 5 cases, no significant effect was achieved. All the 6 patients had severe developmental delay. They could not sit alone, follow the light and objects and had no language.@*Conclusions@#The mutation of KCNT1 gene is mainly de novo. The onset of the disease was early, and mostly occurs in neonate and early infancy. The main seizure type was epilepsy of infancy with migrating focal seizure. Patients usually had severe psychomotor developmental delay. Antiepileptic drugs are ineffective. The efficacy of quinidine was not significant. Though, it still need studies on a large sample.
ABSTRACT
Epilepsy of infancy with migrating focal seizure (MFEI) is an early-onset epileptic encephalopathy characterized by randomly migrating focal seizures and psychomotor deterioration. It is associated with mutations in a variety of genes, with potassium sodium-activated channel subfamily T member 1 (KCNT1) being an example. Previously reported KCNT1 mutations in MFEI are gain-of-function mutations. Therefore, quinidine therapy targeted at reduction of pathologically increased KCNT1 channel-mediated potassium conductance has been proposed as a target treatment for MEFI with KCNT1 mutation. The authors report a case involving a patient with MFEI and a missense mutation in KCNT1 (c.7129G>A; p.Phe346Leu) treated with quinidine therapy. Seizure activity was poorly responsive to quinidine.
Subject(s)
Humans , Brain Diseases , Epilepsy , Mutation, Missense , Potassium , Quinidine , SeizuresABSTRACT
Aim To establish an in vitro early drug cardiac tox-icity evaluation method by human embryonic stem cells derived cardiomyocytes ( hESC-CM) and real-time cell analysis Cardio (RTCA Cardio) system. Method The hESC-CM were cultured at RTCA Cardio E-Plate 96. Impedance signals from hESC-CM were analyzed for beating rate, contraction amplitude and beating rhythm irregularity to determine the optimum inoculation density and detection duration. Based on this, we used 0. 1 % DMSO to be the solvent and quinidine (0. 2, 0. 78, 3. 13, 12. 5, 50 and 100 μmol·L - 1 ) known as affecting cardiac activity to validate this method. Result The results revealed no significant changes in the cell index (CI), transient pulse patterns, beating rate and amplitude of hESC-CM. Quinidine will affect the CI and transi-ent pulse patterns of hESC-CM and decrease the beating rate and amplitude of hESC-CM when its concentration ≥3. 13 μmol · L - 1 . And this effect is concentration-dependent, the higher the concentration,the more time they need to recover beating and the more significant the beating rate and amplitude inhibition of quinidine on hESC-CM. Conclusion The method established by hESC-CM and RTCA Cardio system can detect the effect of quinidine on the contraction of hESC-CM, and this indicates that this method has the potential to be an attractive high-throughput tool for screening potential drugs in early evaluation of drug car-diotoxicity.
ABSTRACT
Aims: To report three cases of successful treatment of tardive dyskinesia (TD) with dextromethorphan. Study Design: Retrospective chart review. Place and Duration of Study: Private outpatient practice in Syracuse, NY. Methodology: A retrospective chart review of patients with TD who were treated with dextromethorphan between 2003 and 2013 was conducted. Results: Three consecutive patients experienced marked improvement of TD with dextromethorphan. Conclusion: Dextromethorphan may be a useful drug for treating TD. Further prospective studies are needed.
ABSTRACT
OBJECTlVE To establish a real-time cell analysis system ( RTCA) for early drug car-diotoxicity evaluation. METHODS An in vitro drug cardiotoxicity evaluation method was established using RTCA Cardio system and primary cultured cardiomyocytes of neonatal rats. The beating rate, am-plitude and beating rhythm irregularity ( BRl ) of cardiomyocytes were observered after antiarrhythmic drugs, such as quinidine and lidocaine were added, to assess the effect of the above method on cardio-toxicity evaluation. RESULTS RTCA Cardo E-Plate 96 was inoculated with primary cultured cardiomyo-cytes that began to beat after 24 h and beat regularly after 48 h. The stable beating was maintained for a minimum of three days. The beating of cardiomyocytes decreased rapidly from 155±5 to 0 after incuba-tion with quinidine. The beating recovered gradually after 6 h. Quinidine at 3.1μmol·L-1 caused the beat-ing rate to return to 124±16. Quinidine allowed the beating rate to return to normal when the concentra-tion was less than 100.0μmol·L-1 . The beating rate, amplitude and BRl of cardiomyocytes changed in a concentration-dependent manner when incubating with lidocaine. The higher the concentration, the more significant the inhibition of lidocaine on cardiomyocytes. CONCLUSlON The cardiotoxicity of quinidine and lidocaine can be detected accurately using RTCA Cardio system, suggesting that this system can be used in early evaluation of drug cardiotoxicity.
ABSTRACT
Investigation of charge-transfer (CT) complexes of drugs has been recognized as an important phenomenon in understanding of the drug-receptor binding mechanism. Structural, thermal, morpholo-gical and biological behavior of CT complexes formed between drug quinidine (Qui) as a donor and quinol (QL), picric acid (PA) or dichlorodicyanobenzoquinone (DDQ) as acceptors were reported. The newly synthesized CT complexes have been spectroscopically characterized via elemental analysis;infrared (IR), Raman, 1H NMR and electronic absorption spectroscopy; powder X-ray diffraction (PXRD);thermogravimetric (TG) analysis and scanning electron microscopy (SEM). It was found that the obtained complexes are nanoscale, semi-crystalline particles, thermally stable and spontaneous. The molecular composition of the obtained complexes was determined using spectrophotometric titration method and was found to be 1:1 ratios (donor:acceptor). Finally, the biological activities of the obtained CT complexes were tested for their antibacterial activities. The results obtained herein are satisfactory for estimation of drug Qui in the pharmaceutical form.
ABSTRACT
BACKGROUND AND OBJECTIVES: Drug-induced electrocardiographic QT interval prolongation is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia, termed 'torsades de pointes' (TdP). Women are at greater risk for the development of drug-induced TdP. To determine whether this may be the result of gender-specific differences in the effect of quinidine on cardiac repolarization, we compared the degree of quinidine-induced QT interval lengthening in young, healthy volunteers. SUBJECTS AND METHODS: Twelve women and 12 men each received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blinded, randomized crossover trial. Total plasma concentrations of quinidine were measured, and QT and corrected QT intervals were analyzed. RESULTS: As expected, the mean QTc interval at baseline was longer for women than for men (443.6+/-26.9 vs 402.1+/-31.3 msec, respectively, p=0.037). The mean value of the maximal DeltaQTc after quinidine infusion was higher in women (134.4+/-46.4 vs 117.5+/-37.7 msec, respectively, p=0.029), and the mean value of the minimal DeltaQTc for 1 hour after quinidine infusion was also higher in the female group (47.6+/-15.7 vs 83.7+/-25.4 msec, p=0.034). However, there were no significant differences in the time courses of the changes in the quinidine-induced QTc and DeltaQTc interval between the two groups (p=0.092, and p=0.305, respectively). CONCLUSION: Quinidine causes greater QT prolongation in women at equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced TdP observed in women taking quinidine, and has implications for other cardiac and noncardiac drugs that prolong the QTc interval.
Subject(s)
Female , Humans , Male , Asian People , Electrocardiography , Healthy Volunteers , Incidence , Plasma , Quinidine , Tachycardia, VentricularABSTRACT
BACKGROUND: Atrial fibrillation (Af) after open heart surgery may result in hypotension, heart failure, embolic complication and prolongation in length of hospital stay. Several studies have investigated the efficacy of pharmacological prophylaxis in reducing the incidence of Af after cardiac surgery. The pericardial sac represents a natural physical barrier and provides a drug receptacle to restrict drug delivery to the heart. The overall objective of this study was to determine whether the pericardial sac could function as a delivery chamber for antiarrhythmic drugs. We investigated whether quinidine delivered into the pericardial sac exerted an effect on atrial and ventricular refractoriness, impulse generation, and conduction. METHODS: All animals were anesthetized with alpha-chloralose. After a sternotomy, the pericardium was opened and cradled to produce a "container" of approximately 30 ml. Experimental animals received quinidine, 3.33 mg/ml, dissolved in Krebs-Henseleit solution instilled into their pericardial sacs for 30 minutes. Baseline and 5, 10 and 30 minutes postinstillation electrophysiologic studies were performed. Plasma quinidine levels were measured at each of the time intervals in three different sites i.e., right ventricle (RV), aortic root and femoral vein (FV). RESULTS: Baseline systolic (SAP) and diastolic aortic pressure (DAP) were 148+/-16.8 mmHg, and 111+/-23.9 mmHg, respectively. Both SAP and DAP were significantly decreased at 5, 10 and 30 minutes after instillation of quinidine solution into pericardial sac. In electrocardiographic parameters, the increase in sinus cycle length and corrected QT interval were significantly greater compared with baseline at each of the time intervals after instillation of quinidine solution into pericardial sac. All electrophysiologic parameters including 1:? AV conduction, effective refractory period (ERP) of RA and RV were significantly increased compared with baseline at three time points. Quinidine concentrations in RV and aorta were significantly higher than in FV at three time points. In RV and aorta, quinidine concentrations at 30 min were significantly lower than those at 5 and 10 min postinstillation periods. There were significant correlations between plasma quinidine levels and corrected QT interval or RAERP. CONCLUSION: Above results showed that quinidine instilled into the pericardial sac migrates transmurally and produces significant prolongation of effective refractory period and may appear to prevent various arrhythmias including atrial fibrillation after cardiac surgery.
Subject(s)
Animals , Anti-Arrhythmia Agents , Aorta , Arrhythmias, Cardiac , Arterial Pressure , Atrial Fibrillation , Chloralose , Electrocardiography , Electrophysiology , Femoral Vein , Heart , Heart Failure , Heart Ventricles , Hypotension , Incidence , Length of Stay , Pericardium , Plasma , Quinidine , Sternotomy , Thoracic SurgeryABSTRACT
The constant iv. of aconitine can induce the varied arrhythmias in mice. Taurine 100mg/kg iv. or Quinidine 5 mg/kg iv. can delays the onset time of arrhythmias, and increases the dose of aconitine, respectively .But no effects were seen in mice pretreated with taurine 50mg/kg or quinidine 2.5mg/kg. However their combination can significantly decrease the incident of ventricular fibrillation and delay the onset time of death. Our results suggested that taurine, quinidine and their combination are effective on arrhythmias induced by aconitine in mice.
ABSTRACT
The content of malondialdehyde (MDA) , a metabolite of lipid peroxide (LPO) , in plasma and tissue homongenate from rabbits with arrhythmias induced by adrenaline (Adr) was determined. The results showed that the MDA level was increased in plasma and tissue homogenate. Quinidine (Qui) 6 mg ? kg-1, Cimetidine (Cim) 37. 5 mg?kg-1, and 1/2 dose of both drugs administered intravenously couldsignificantly prevent ventricular arrhythmias induced by Adr and inhibit the production of MDA. The findings suggest that the effect of Qui and Cim on arrhythmias induced by Adr may associate with its inhibition on lipid peroxi-dation.
ABSTRACT
Neferine, an alkaloid, isolated form Nelumbo nucifera Gaertn,has antiarrhytbmic effect. The present report deals with its action on the ECG in rat & the surface potential of toad sciatic nerve.Neferine could prolong ECG, P-R & Q-T intervals, and widen QRS in a dose-dependent manner, The effects are similar to quini-dine, and dissimilar to tetrandrine. The inhibitory effects of neferine & quinidine on the surface potential of toad sciatic nerve are similar in potency.
ABSTRACT
Tetrandrine, a bis-benzy 1-i soqui noline alkaloid isolated from Radix Stephania tetrandra S. Moor, was proved to be a calcium antagonist. Its effects upon the heart conduction system were investigated in anesthetized rabbits.Tetrandrine 8 mg/kg iv could prolong the sino-atrial conduction time & the sinus node recovery time from 50 ? 13 ms & 286? 36 ms to 75?19 ms ( n= 8 , P