Study on fluvoxamine maleate sustained-release pellets and its compression technology / 药学学报

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

A Report of Rabbit Syndrome Who Benefited from Sigma 1 Agonist Fluvoxamine

Rabbit Syndrome is an uncommon side effect of antipsychotic treatment. Although it is usually associated with typical antipsychotics, it can also be related to atypical antipsychotics. Anticholinergics are the most accepted treatment approach in treating Rabbit Syndrome. Fluvoxamine is a member of selective serotonin reuptake inhibitors and it is a potent agonist of sigma 1 receptors. In this article, we report a Rabbit Syndrome case who has benefited from fluvoxamine, in terms of both depressive disorder and Rabbit Syndrome; and present the data on the effects of sigma 1 agonist fluvoxamine on numerous movement disorders.

Fluvoxamine-induced intracranial hypertension in a 10-year-old boy

Drug-induced intracranial hypertension is a well-established entity. We report a rare case of intracranial hypertension with papilledema in a 10-year-old boy following use of fluvoxamine, a selective serotonin reuptake inhibitor. On discontinuing the drug, the papilledema resolved over 4 months without any residual visual anomalies. To the best of our knowledge, this is the first report of fluvoxamine-induced intracranial hypertension with papilledema.

Determination of Fluvoxamine in Human Plasma by FPLC-MS/MS / 中国药师

Objective:To establish an FPLC-MS/MS method for the determination of fluvoxamine in human plasma. Methods:The separation was performed on an Inertsil? ODS-SP column(2. 1 × 100 mm, 3 μm). The mobile phase was acetonitrile-2 mmol· L-1 ammonium acetate (45: 55, v/v) containing 0. 1% formic acid at a flow rate of 0. 3 ml·min-1 . Lansoprazole was used as the internal standard( IS) . Electrospray ionization ( ESI) source was applied and operated in a positive ion model. Multiple reaction moni-toring (MRM) model with the transitions of fluvoxamine m/z 319. 1→m/z 69. 8 and lansoprazole m/z 370. 2→m/z 252. 1 was used to quantify fluvoxamine and IS, respectively. Results:In human plasma, the standard curve was linear within the range of 1-100 μg· L-1 . The lower limit of quantification of fluvoxamine( LLOQ) was 1μg·L-1 . The intra-day RSD was less than 5%, the inter-day RSD was less than 10%, and the method recovery was 85%-95%. Conclusion:The method is simple, sensitive, accurate and reproduci-ble. It is applicable in the pharmacokinetic study of fluvoxamine for clinical pharmacokinetics and bioequivalence studies.

Determination of Fluvoxamine in Human Plasma by FPLC-MS/MS / 中国药师

Objective:To establish an FPLC-MS/MS method for the determination of fluvoxamine in human plasma. Methods:The separation was performed on an Inertsil? ODS-SP column(2. 1 × 100 mm, 3 μm). The mobile phase was acetonitrile-2 mmol· L-1 ammonium acetate (45: 55, v/v) containing 0. 1% formic acid at a flow rate of 0. 3 ml·min-1 . Lansoprazole was used as the internal standard( IS) . Electrospray ionization ( ESI) source was applied and operated in a positive ion model. Multiple reaction moni-toring (MRM) model with the transitions of fluvoxamine m/z 319. 1→m/z 69. 8 and lansoprazole m/z 370. 2→m/z 252. 1 was used to quantify fluvoxamine and IS, respectively. Results:In human plasma, the standard curve was linear within the range of 1-100 μg· L-1 . The lower limit of quantification of fluvoxamine( LLOQ) was 1μg·L-1 . The intra-day RSD was less than 5%, the inter-day RSD was less than 10%, and the method recovery was 85%-95%. Conclusion:The method is simple, sensitive, accurate and reproduci-ble. It is applicable in the pharmacokinetic study of fluvoxamine for clinical pharmacokinetics and bioequivalence studies.

Evaluation of an anti-diuretic activity of fluvoxamine in albino rats.

Background: Diabetes insipidus is a disease characterized by high amounts of urine excretion. Antidiuretic drugs are used to treat this condition. Hence, our study intends to evaluate the anti-diuretic effect of fluvoxamine, a selective serotonin reuptake inhibitors in albino rats. Methods: Albino rats were divided into three groups of six animals each. The control group was fed with distilled water 10 ml/kg body weight, standard group received 4 units of vasopressin and test group received fluvoxamine 18 mg/kg body weight. On the day of experiment, diuresis was induced in all the groups by giving frusemide in a dose of 20 mg/kg body weight after loading with saline at 25 ml/kg body weight. The animals were confined in diuretic cage for a period of 5 hrs and urine output was noted. Urine was analyzed for electrolyte concentration (Na+, K+, Cl−). Results: There was significant reduction in urine output in the test group of animals when compared to the control group. Electrolyte concentration revealed relatively concentrated urine when compared to the control group. Conclusions: Fluvoxamine has a significant anti-diuretic action in the albino rats.

Effects of calcium channel blocker, nifedipine, on antidepressant activity of fl uvoxamine, venlafaxine and tianeptine in mice.

Background: Cardiovascular diseases are commonly associated with depression. Calcium channel blockers (CCBs) form commonly used group of drugs for the treatment of a number of cardiovascular diseases. Nifedipine, a CCB, has been shown to possess antidepressant activity and potentiate antidepressant activity of imipramine and sertraline, however, literature on its interaction with newer antidepressant drugs such as fl uvoxamine, venlafaxine and tianeptine is limited. Hence, the present study was undertaken. Methods: The study was carried out in albino mice in two phases. In Phase I, antidepressant activity of nifedipine, fl uvoxamine, venlafaxine and tianeptine were confi rmed after their single dose administration using forced swim test (FST) and tail suspension test (TST) and their minimum antidepressant doses were determined. In Phase II, the effect of nifedipine on antidepressant activity of fl uvoxamine, venlafaxine and tianeptine was studied by orally administering sub-antidepressant doses of these drugs for 28 days. FST and TST were carried out on 1st, 14th and 28th day of the study and change in immobility period was observed. Results: In Phase I, all the studied drugs exhibited dose dependent antidepressant activity in both FST and TST. Minimal antidepressant dose of nifedipine, fl uvoxamine, venlafaxine and tianeptine was observed as 10, 25, 25 and 10 mg/kg respectively. In Phase II, combinations of sub-antidepressant dose of nifedipine (5 mg/kg) with sub-antidepressant doses of fl uvoxamine (12.5 mg/kg), venlafaxine (12.5 mg/kg) and tianeptine (5 mg/kg) exhibited enhanced antidepressant activity when compared to the control group and individual drug groups after same duration of treatment. Conclusions: Nifedipine, fluvoxamine, venlafaxine and tianeptine possess antidepressant activity and nifedipine exhibits synergistic antidepressant activity with fl uvoxamine, venlafaxine and tianeptine.

Effects of fluvoxamine in the treatment of trichotillomania / 中华行为医学与脑科学杂志

Objective To evaluate clinical efficacy and safety of fluvoxamine in the treatment of trichotillomania.Methods 24 outpatients who met the DSM-Ⅳ diagnosis criteria for trichotillomania received fluvoxamine for 12 weeks and 17 tricholillomania outpatients weren't treated with fluvoxamine.Clinical efficacies and adverse reactions were assessed with the spence children's anxiety scale(SCAS),Kovacs children's depression inventory (CDI),clinical global impression(CGI) and treatnent emergent symptom scale(TESS) before treatment and the end of the 4th and 12th week.Results After 4 weeks treatment,the scores of the SCAS (59.75 ± 12.35),CDI (24.95±7.68) and CGI(SI) (3.79±0.93) were lower than those before treatment(71.50±20.65,31.60± 10.40,5.88±0.68 respectively) (P＜0.05).After 12 weeks treatment the scores of the SCAS,CDI and CGI (SI) were lower than those after 4 weeks treatment (P＜0.05).After 12 weeks treatment the scores of the CGI(GI) (1.54±0.59) were lower than that at the end of 4 weeks treatment (2.96± 0.69) (P＜ 0.05).Conclusion Fluvoxamine has a good efficacy and higher safety in the treatment of trichotillomania.

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent. .

Polypharmacy in a nine year old boy with Attention Deficit Hyperactivity Disorder and Tourette Syndrome: what worsened the ties?

Introduction: Attention Deficit Hyperactivity Disorder(ADHD) and Tourrete Syndrome(TS) commonly co-occur, imposing a special challenge in the management. Case report: This is a case of a nine year old boy with ADHD and TS, who had been on methylphenidate, risperidone, fluvoxamine and atomoxetine, alone and in combination. Tics worsened with methylphenidate but improved after its withdrawal, and the addition of risperidone and fluvoxamine. Later, atomoxetine was added which worsened the tics, even when it was removed. Significant improvement in the tics were only obvious when fluvoxamine was taken off. Discussion: The possible roles of dopamine and serotonin neurotransmission, and metabolism of cytochrome P450 D26 in the pathophysiology were discussed. Conclusion: The use of multiple medications need cautious consideration and monitoring in a child patient to avoid unwanted complications and risks.

A case report of a bipolar disorder patient with severe lithium poisoning possibly induced by interaction between risperidone, telmisartan, fluvoxamine and lithium.

We describe a case of severe lithium poisoning possibly induced by multiple drug interaction. A 45-year-old man with bipolar disorder was admitted with altered behavior and mental status. He was maintained on lithium for 20 years. Nine months ago, lithium dose was increased and risperidone was added. Telmisartan was prescribed around 25 days ago and he had mild tremor since then. Two days ago, fluvoxamine was initiated and he developed restlessness, agitation, insomnia and confusion after one dose. On admission, fluvoxamine, lithium, telmisartan and risperidone were discontinued. Abnormal findings were temporary ST depression, hyponatremia and high creatine kinase. He had fever since day 2 and was covered for meningoencephalitis and neuroleptic malignant syndrome. On the next day, he was comatose and treated for septic shock. On day 7, result of serum lithium taken on day 3 revealed severe toxicity (3.2 mEq/L). The lithium level was normalized after hemodialysis. He subsequently regained full Glasgow Coma Scale score and his toxicity completely resolved on day 16. Interactions of risperidone and telmisartan with lithium possibly precipitated the lithium toxicity. However, the onset of the toxicity suggested fluvoxamine as the major cause of poisoning. Clinicians should be aware of these potential drug interactions.

Benefical Effects of Sigma-1 Agonist Fluvoxamine for Tardive Dyskinesia and Tardive Akathisia in Patients with Schizophrenia: Report of Three Cases

Fluvoxamine is a selective serotonin reuptake inhibitor that is approved for psychiatric disorders such as major depressive episodes and obsessive-compulsive disorder. Beside inhibition of serotonin reuptake, fluvoxamine is also a potent agonist of endoplasmic reticulum (ER) protein sigma-1 receptors, which play a role in the pathophysiology of a number of psychiatric and neurodegenerative disorders. This report presents beneficial effects of sigma-1 agonist fluvoxamine on hyperkinetic movement disorders such as tardive dyskinesia and tardive akathisia. Fluvoxamine might be a novel treatmet approach in the treatment of hyperkinetic movement disorders.

Spectral and electrochemical studies of fluvoxamine.

The spectral and voltammetric behavior of fluvoxamine (1) in aqueous buffers of varied pH is presented. Spectrophotometry, cyclic voltammetry, differential pulse polarography and coulometry were utilized to study its proton and electron transfer characteristics. Relevant thermodynamic and electrochemical data such as charge transfer coefficient (αna), heterogeneous forward rate constant (k0 f,h), etc, have been evaluated. An excellent electroanalytical assaying of 1 has been developed in differential pulse polarography at pH = 3. Molecular modeling on various acid-base conjugates of 1 and their several conformers has been carried out to arrive at the thermodynamic and conformational issues to correlate to the spectral and electrochemical observations.

Spectrophotometric determination of fluvoxamine as maleate by selective methods.

Simple, accurate and reproducible visible spectrophotometric methods for the assay of drug fluvoxamine as maleate were established based on the formation of oxidative coupling reaction between the corresponding drug, Brucine-NaIO4 and DCQC. The procedures described were applied successfully to the determination of the compound in their dosage forms. The results showed that the proposed procedures compared favorably with the reference methods and satisfactory sensitivity, accuracy and precision. The optical characteristics such as Beer’s law limits, molar absorptivity and sandell’s sensitivity are reported. Regression analysis using the method of least squares was made to evaluate the slope (b), intercept (a) and correlation coefficient (r) and standard error of estimation (Se) for the drug.

Compulsive masturbation treated with fluvoxamine-a case study

Masturbation is a normal part of psychosexual development. It becomes troublesome when it becomes ego-dystonic &compulsive in nature. The present article reviews the literature available on compulsive masturbation and provides acase report of a middle aged male who presented with compulsive masturbation and was treated successfully withfluvoxamine.

Changes of Functional MRI Findings in a Patient Whose Pathological Gambling Improved with Fluvoxamine

Legalized gambling is a growing industry, and is probably a factor in the presently increasing prevalence of pathological gambling. We present a case of a 36-year-old pathological gambler who was treated with fluvoxamine, a selective serotonin reuptake inhibitor, and who was assessed by functional MRI before and after drug administration. During activation periods, the pathological gambler was shown cards as stimuli, and fMRI results in several brain regions showed differential effects before and after medication and a maintenance period. This case demonstrates that the treatment response to fluvoxamine in a pathological gambler was observed not only by subjective self-report, but also by objective fMRI results. Therefore, fMRI may be a useful tool in the diagnosis and prediction of treatment response in patients afflicted with pathological gambling.

Application of fluvoxamine in psychiatry / 医学研究生学报

The paper primarily reviewed fluvoxamine's efficacy on depression,anxiety disorder and body dysmorphic disorder,and reviewed fluvoxamine′s drug adverse effect,pharmacokinetics,dose and drug interaction.